Radioisotopes: A Market In Decay?

April 19, 2010

Radioisotopes are used in everything from smoke detectors to cancer treatments. But is a supply crunch on the way?
  • What is a radioisotope, and how is it used?
  • How do you make a radioisotope?
  • Ways to play an increasingly small supply

 

Radioisotopes, or unstable versions of an element that emit radiation as they try to reach a more stable form, are critical in modern medicine:

"99Mo is used to produce 99Mo/99mTc generators (a generator technology developed at Brookhaven National Laboratory) for use in nuclear medicine. 99mTc is the most widely used radionuclide in nuclear medicine, both for the detection of disease and for the study of organ structure and function. More than 15 million procedures are performed each year in the U.S. using 99mTc."

                                                                Isotopes for the Nation's Future  A long range plan      

                                                                U.S. Nuclear Science Advisory Committee — Aug. 27, 2009

 

However, the U.S. produces none of the radioisotope molybdenum-99 (99Mo), from which comes the radioisotope technetium-99m (99mTc). Indeed, none has been produced in the country since 1988.

99mTc is so important that it is used in more than 80 percent of all nuclear medicine diagnostics and studies of organ structure and function. Not only is the figure of 15 million, quoted above, probably too small, but the number of procedures using 99mTc in the U.S. alone probably accounts for a half, if not more, of the 35 million such procedures carried out globally each year.

 

A Short Guide To Isotopes

The simplest way to envisage an atom is to imagine a nucleus, which consists of protons and neutrons, surrounded by a cloud of electrons. The number of protons in the nuclei of any element's atoms determines the chemical character of that element.

Different isotopes of an element all contain the same number of protons, but different numbers of neutrons and, hence, have different atomic masses. While some isotopes are stable, others are not: For the 82 stable elements, there are around 275 associated stable isotopes and 1,800 unstable isotopes or radioisotopes. (The U.S. Nuclear Science Advisory Committee (NSAC), in the report quoted above, estimates the number of natural and artificial radioactive isotopes as exceeding 3,200 and "...growing every year.")

The nuclei of unstable isotopes usually stabilize through radioactive decay (hence the name "radioisotope"). That is, as the isotope tries to reach a more stable form, it kicks off alpha particles—two protons and two neutrons—and/or beta particles, which are electrons or positrons. These beta particles are often (but not always) accompanied by the emission of gamma rays or electromagnetic radiation.

Unstable isotopes rarely occur in nature and are nearly always produced artificially. For example, 99mTc is produced as the artificially produced radioisotope 99Mo decays, which decays through gamma ray emission (and a rearrangement of its nucleus) to become 99Tc.

 

Using Radioisotopes

Radioisotopes, either naturally occurring or artificially produced, are useful because they emit radiation, whether alpha, beta or gamma. You're probably familiar with carbon dating, which uses a naturally occurring isotope of carbon, 14C (carbon-14); 14C can measure the age of water up to 50,000 years old. But it may come as a surprise that, according to the Australian Nuclear Science and Technology Organisation (ANSTO), smoke detectors represent "the largest number of devices based on radioisotopes used world-wide." (The devices use a minute quantity of 241americium, which is a product of the decay of plutionum-241.)  

Around 200 different radioisotopes are currently used in a variety of applications, such as in food and agriculture, industry or medicine.

 

Food And Agriculture

In food and agriculture, the radiation emitted by radioisotopes is used in a variety of different ways.

  • Insect Eradication
    Each year, insects probably destroy around 10 percent of global harvests. In developing countries, this figure has been put as high as 25-35 percent. In what is called the sterile insect technique (SIT), huge numbers of insects are bred, irradiated with gamma rays to sterilize them, and then released en masse in infested areas. Since they are sterile, they cannot reproduce and, subsequently, after a series of such releases, the insect populations in the areas in which they are released can be decimated. SIT has been used successfully against such insects as the Mediterranean fruit fly (in Argentina, Chile and Mexico), the screwworm (in Mexico and the southern U.S.) and the tsetse fly (in Africa).
  • Food Preservation
    Irradiation, using gamma rays, is now an accepted method of destroying bacteria, insects and various harmful organisms in a number of different foodstuffs, e.g., cereals, fresh fruit, seafood and vegetables. Indeed, it is the only way to kill bacterial pathogens in frozen and raw food.
  • Fertilizer Labeling
    When used as labels, the two radioisotopes, nitrogen-15 (15N) and phosphorus-32 (32P), can indicate how much fertilizer is taken up or lost by plants.
  • Genetic Alteration
    Either gamma or neutron irradiation can be used to help with genetic modification and the production of strains of plants that are either more productive or resistant to pests.
  • Sterilization
    Gamma rays are also used to sterilize such things as archival documents, wood and raw wool (before it is exported from Australia).

 

Industry

Radioisotopes also have a range of industrial uses, including:

  • Nuclear Gauging
    Beta radiation can be used to gauge (and control) the thickness of anything from continuous sheets of paper to metal, glass and plastic film as they speed through the machinery that makes them. In the coal industry, gamma radiation is used not only to measure the ash content of coal as it passes on line, but also its sulfur and moisture contents. And when the coal is in its hoppers, gamma radiation is used to gauge exactly how full the hoppers actually are. In addition, radioisotopes are used in both borehole logging and, more simply, to measure the water content of soil and its density.
  • Gamma Radiography
    Gamma rays can be used to produce images much in the same way X-rays are. However, gamma rays can produce not only an image of the object through which they are passing, they can also help provide a degree of analysis of the object itself. This is one reason why gamma radiography is often used to screen luggage at airports. More mainstream uses of gamma radiography include weld inspection in gas and oil pipelines using "pipe crawlers," and stress testing, e.g., of the structural integrity of jet turbine blades. Autoradiography and neutron radiography can also be used to locate things that might otherwise be difficult to see, e.g., detecting corrosion and moisture entrapment, especially in aircraft structures.
  • Tracing
    Since the tiniest amount of a radioactive material can be easily traced, radioisotopes are ideal when conditions are either particularly harsh or complex. Measuring liquid flows through, for instance, a blast furnace is an example of the former. Using a radioisotope to detect leaks in, say, a power station is an instance of the latter. One other fascinating example is provided by the World Nuclear Association in their paper "Radioisotopes in Industry": "The extent of termite infestation in a structure can be found by feeding the insects radioactive wood substitute, then measuring the extent of the radioactivity spread by the insects. This measurement can be made without damaging any structure as the radiation is easily detected through building materials."

 

Some common industrial radioisotopes include:

Radioisotope Half-Life Decay Some Uses
Carbon-14* 5,730 yrs Beta Dating. Tracer in photosynthesis studies.
Chlorine-36* 301,000 yrs Beta Measuring age of water - up to 2 million years
Hydrogen-3* (tritium) 12.32 yrs Beta Measuring age of "young" (up to 30 years) groundwater. In red building exit signs.
Lead-210* 22.3 yrs Beta Dating layers of sand and soil up to 80 years old
Americium-241 432 yrs Alpha Smoke alarms and neutron gauging
Caesium-137 30.2 yrs Beta Tracing and thickness gauging
Cobalt-60 5.3 yrs Beta Gamma radiography, gauging and sterilization
Gold-198 2.69 days Beta Tracing factory waste pollution in oceans
Iridium-192 73.83 days Beta Gamma radiography
Krypton-85 10.76 yrs Beta Industrial gauging and locating leaks
Magnesium-27 9.5 mins Beta Locating leaks
Manganese-54 312.2 days Gamma Predicting the behavior of heavy metals in effluents from mining waste water
Nickel-63 100.1 yrs Beta Light sensors in cameras and thickness gauging
Selenium-75 119.78 days Gamma Gamma radiography and nondestructive testing
Sodium-24 15 hrs Beta Locating leaks
Strontium-90 28.8 yrs Beta- Thickness gauging
Ytterbium-169 32 days Gamma Gamma radiography
Zinc-65 244.26 days Gamma Predicting the behavior of heavy metals in effluents from mining wastewater

*Naturally occurring

Beta- is positron emission

 

Medicine

As mentioned before, radioisotopes are key in modern nuclear medicine. Three of their most important uses are:

  • Sterilization
    Many medical devices that cannot be sterilized in any other way are sterilized using gamma radiation. This applies, in particular, to single-use devices such as gloves, syringes (and needles), alcohol wipes and scalpel blades. In addition, irradiation is used to sterilize plasma, serum and tissue that is going to be transplanted.
  • Medical Diagnostics
    Some 10,000 hospitals around the world use radioisotopes for diagnostic tests. Taken orally, inhaled or injected, medical isotopes are used in a wide variety of different procedures. They are used, for example, to assess bone damage; how hearts, kidneys, livers and lungs are functioning; and, extensively, for testing for cancer, heart and thyroid diseases. On a more mundane level, they are commonly used in biochemical analyses in vitro (known as radioimmuno-assays) to test blood, urine, hormones and serum, among other biological samples. Some 15 million such analyses are undertaken each year in Europe alone.[1]
  • Medical Treatments
    Irradiation can control or even eliminate some cancerous growths. Some radioisotopes, for example, strontium-89 and samarium-153, are excellent for reducing pain induced by certain cancers. Tiny seeds, or sometimes wires, of radioisotopes are used in the treatment of various cancers found in the breast, head, prostate and thyroid. (Interestingly, however, the frequency of use of radioisotopes in therapeutics is only about a tenth of their use in diagnosis.)

 

Some commonly used isotopes in medicine include:

Radioisotope Half-Life Decay Some Uses
Bismuth-213 46 mins Alpha Cancer therapy
Cobalt-60 5.27 yrs Gamma Sterilization
Erbium-169 9.4 days Beta- Relief of pain from arthritis
Iodine-125 60 days Gamma Treatment of brain and prostate cancer
Phosphorous-32 14 days Beta Treatment of excess red blood cells
Technetium-99m 6 hrs Gamma Many different imaging applications
Thallium-201 73 hrs Gamma Diagnosis of coronary artery disease
Xenon-133 5 days Beta- Pulmonary ventilation studies

Beta- is positron emission

 

Radioisotope Production

Although a number of radioisotopes occur naturally, most of the 200 used on a regular basis are produced artificially. This mainly occurs via three methods: nuclear reactors; research reactors; and cyclotrons and linear accelerators.

Nuclear Reactors

Although not the most common source of radioisotopes, a number of power reactors do produce radioisotopes. Put at its simplest, isotopes are made in a nuclear reactor through neutron gain; that is, some of the million errant neutrons winging around inside the core of the reactor are absorbed by the nuclei of particular materials placed in the reactor's core. So, for example, if one of cobalt's stable isotopes, cobalt-59, is stuck in the core of a nuclear reactor and exposed to a high flux of neutrons, it can absorb some of these neutrons (adding one to each of its nuclei) and become the radioisotope cobalt-60.

Research Reactors

Currently, radioisotopes are most commonly produced in research reactors through fission, or the splitting of the nuclei in atoms. Rather than neutrons being absorbed by the nuclei of other atoms, they are instead hurled at those other atoms to break up their nuclei and create byproducts in the form of radioisotopes. The speed of these neutrons and the temperature will determine exactly which radioisotopes are produced.

Cyclotrons And Linear Accelerators

Lastly, radioisotopes can be produced in either cyclotrons or linear accelerators. In both of these, a beam of protons is accelerated, using magnets, and smashed into a target to produce the required radioisotope. One major difference between using a cyclotron and a nuclear reactor is that a cyclotron needs neither fissionable material nor uranium to produce radioisotopes. On the other hand, however, it can only accelerate charged particles and only protons can be added in this way to atomic nuclei.

In fact, while reactors produce neutron-rich nuclei, cyclotrons and linear accelerators, by adding protons, produce neutron-deficient nuclei. Because neutron-deficient and neutron-rich radioisotopes decay by different means, they will have different properties and are better suited for different purposes.

 

Most Widely Used Radioisotopes

By far the most widely used radioisotopes, excluding those used in power production, are three used for medical purposes: cobalt-60, technetium-99m (molybdenum-99) and thallium-201—in that order.

A 2008 paper by Lawrence Kidd in Nuclear Engineering International estimated total yearly global production of cobalt-60 at 60 million curies, while production of molybdenum-99/technetium-99m was some 468,000 6-day curies.[2]

While these figures may reflect how things were back in July 2008, the scene has changed radically since Kidd published his groundbreaking article just over 18 months ago.

Both cobalt-60 and molybdenum-99 are produced in reactors. But perhaps surprisingly, both radioisotopes are produced only in a handful of power and research reactors, a couple of which have now not been operating for quite some time. This has recently led to a major supply crisis for molybdenum-99 and, hence, technetium-99m.

Before it closed for repairs last May, the National Research Universal (NRU) reactor probably produced more than 80 percent of the world's cobalt-90 and nearly 40 percent of its molybdenum-99. Today it produces nothing. The latest update indicates that only some 56 percent of the repair work necessary to return the reactor to services has been completed.

Then, in late February, the high flux reactor (HFR) at Petten in the Netherlands, which is estimated to have produced 25 percent or more of the world's molybdenum-99, was also shut down for repairs. This reactor is not expected to start operating again until at least August 2010.

Some of the world's major radioisotope-producing reactors include:

Radioisotope Source Country
Cobalt-60 Atucha 1 Argentina
Embalse Argentina
Bruce B 1 and 2 Canada
NRU Canada
Qinshan 1 China
Leningrad 1 Russia
Wolsong 1 South Korea
Clinton BWR U.S.
Molybdenum-99 BR-2 Belgium
HFR The Netherlands
NRU Canada
Osiris France
Maria Poland
Safari-1 South Africa

Source: World Nuclear Association

 

According to the World Nuclear Association, some 90 percent of the world's molybdenum-99 was made by NRU and HFR, with the rest coming from the BR-2, Safari-1 and Osiris reactors (7 percent). (For the most part, the isotope results from fission of highly enriched uranium-235 targets, which are then processed to separate the molybdenum-99.)

What's more, there are equally as few "large-scale producers" of molybdenum-99 (using the term "large-scale producers" of molybdenum-99, as in Medical Isotope Production Without Highly Enriched Uranium, to describe one that supplies "...more than 1000 6-day curies of Mo-99 per week to the market on a routine basis"). Essentially, only four producers—MDS Nordion, Covidien, IRE and NTP—account for the entire market: MDS Nordion accounts for 40 percent of the market, Covidien 25 percent, IRE 20 percent, NTP 10 percent and others just some 5 percent.

 

Medical Isotope Demand

Mo-99

While the World Nuclear Association puts current global demand for molybdenum-99 at 621,000 curies, the Committee on Medical Isotope Production Without Highly Enriched Uranium of the U.S. National Research Council (using 2006 figures) estimates current demand in the U.S. to be 5,000-7,000 6-day curies per week. The committee envisages that: "Demand growth for Mo 99/Tc-99m in the United States over the next 5 years could range from 0 to 5 percent per year with the most likely growth rate in the range of 3 to 5% per year."

Whatever the current demand figures may be, however, it is generally recognized that, with demand increasing, the precariousness of the supply of Mo-99 is becoming ever-more apparent. Not only does the majority of the world's supply come from just five reactors, but also, as of mid-2010, they will all be some 43-52 years old. And while the remaining reactors can take up some of the slack when major reactors go "off line," it does not answer the question as to whence Mo-99 will, in the long term, come. Adequacy and reliability of supply are both of particular importance in the instance of Mo-99, as it is such a short-lived isotope.

Covidien, in its search for alternative sources of Mo-99, announced in March 2010 that both U.S. and Canadian health officials had approved its use of Mo-99 sourced from the Maria Research Reactor (one of the most powerful in the world) some 30 kilometers southwest of Warsaw in Poland.

Co-60

In the current absence of production of cobalt-60 from Canada's NRU reactor, production has been expanded not only at Bruce 1 and 2 in Canada, but also in China, Russia and South Korea, with a noticeable increase in availability from the Leningrad 1 reactor in Russia.

In the U.S., cobalt-60 is currently only produced (in conjunction with International Isotopes, Inc.) in one location: at the U.S. Department of Energy's Idaho National Engineering and Environmental Laboratory west of Idaho Falls in Idaho. However, in January this year, the Nuclear Regulatory Commission (NRC) approved cobalt-60 production at Exelon Nuclear's Clinton Power Station (a boiling-water reactor) in Dewitt County, Illinois. And in March, Exelon, together with GE Hitachi Nuclear Energy, applied to produce further cobalt-60 in PSEG's Hope Creek reactor in New Jersey. If approval is given by the NRC, this will double the number of U.S. commercial 104 reactors producing the isotope—to two.

Although the situation may be somewhat different with cobalt-60, since it has a half-life of some 5.27 years (as opposed to the six hours of technetium-99m), there are concerns both as to the dwindling stocks of the isotope and the continuing increase in its usage. In the U.S. alone, industry estimates put the proportion of medical tools and syringes sterilized or cleaned using cobalt-90 at around 40 percent. And each year some 50,000 patients go under the Gamma Knife for radiation treatment.

Although lumping all uses of (and demand for) cobalt-60 together is somewhat like making an isotope "fruit salad" (since it is used in a such wide variety of different ways), one industry expert described a supply/demand figure (before Canada's NRU reactor went "off line") of some 60 million curies per year (around the figure estimated by Lawrence Kidd back in 2008) as reflecting a "fairly good balance."

 

Opportunities In Radioisotopes

Back in 2008, Kidd estimated the worldwide value of radioisotope (Co-60, Mo-99, Tl-201 and others) production to be somewhere south of half a billion dollars.

Quite obviously, you can neither invest physically in the space nor in the reactors that irradiate targets to produce the isotopes. In the case of Mo-99, all the radioisotope producers use either government-owned research or test reactors. In the case of Co-60, only when the two commercial reactors start producing the isotope will production have moved out of government hands.

The major isotope producers (of Mo-99 and Co-60), on the other hand, are a mixture of private and publicly quoted companies.

Of the Mo-99 producers, the only publicly quoted ones are MDS Nordion, a division of MDS Inc. (NYSE: MDZ) and Covidien PLC (NYSE: COV). MDS Nordion accounts for 60 percent of the U.S. Mo-99 supply, while COV accounts for the rest.

 

The Global Mo-99 Market

Nuclear Reactors

Source: With data from Medical Isotope Production Without Highly Enriched Uranium

 

Both the Belgian Institut National des Radioelements (IRE) and Nuclear Technology Products (NTP), a division of Necsa Ltd. (the South African Nuclear Energy Corporation) are state-owned. However, for both MDS Nordion and Covidien, radioisotopes are just one part of their businesses.

Further down the supply chain, the Tc-99m generators used in the U.S. are supplied either by MDS Nordion or Massachusetts-based Lantheus. (Lantheus is privately held.)

Of the producers of Co-60, once again MDS Nordion is the largest. Together with Reviss, an Anglo-Russian consortium that sources its cobalt-60 both from within Russia and, more recently, from National Atomic Energy Commission (CNEA) of Argentina, the two dominate the Co-60 radioisotope market. Reviss is a private company, whose majority shareholders are companies within the Russian State Corporation of Atomic Energy (or ROSATOM).

International Isotopes, Inc. (NASDAQ: INIS) contracts with the U.S. Department of Energy to produce cobalt-60 sources, and is, in fact, the only producer of such cobalt in the U.S. In 2009, sales of all its cobalt products accounted for some 36 percent of total sales.

For the producers of radioisotopes and for those companies who supply Mo-99/Tc-99m generators, such business maybe both growing (when the supplies of Mo-99 are there) and profitable, but it is also increasingly precarious. Regarding the small number of reactors that can carry out the requisite irradiation to produce isotopes, their geographical spread across the globe and their age are all serious issues. In a situation where one or more reactor "goes down," sourcing alternative supplies, of which there are few, becomes a critical issue. In addition, currently all these reactors are publicly funded research reactors. The irradiation services they provide are, de facto, heavily subsidized. (Consider alone the commissioning and decommissioning costs of a nuclear reactor.) Whether this will continue is another matter altogether.

Aside from both these quite serious production and economic concerns, and riding above them, there is the whole issue of the use of highly enriched uranium (HEU) - which can also be used to develop nuclear weapons—to produce radioisotopes. (Vide Iran.) One of President Obama's major goals is to reduce the risk posed by the global use of HEU—for whatever purposes. And the production of radioisotopes (even for medical use) is one of the purposes.

Although it has been shown that the use of low enriched uranium (LEU) to produce Mo-99 is quite feasible, and that the costs of conversion to LEU-based production from HEU-based production are not unreasonable, it would appear that alternative methods of Mo-99 production using linear accelerators may not currently be as feasible. (On the other hand, TRIUMF—Canada's national laboratory for particle and nuclear physics—together with MDS Nordion has been looking quite carefully at the use of photo-fission-based production of Mo-99.) One of the main problems at present is that neither any competitive nor any financial reasons exist for industry to undertake this conversion.

If, however, government policy were to change, with the provision of financial incentives (even temporary ones) to encourage either improved capacity or the establishment of new suppliers of LEU-based Mo-99, then some interesting opportunities may arise—not least because it has become increasingly apparent that stability of supply is actually a much more serious problem at present than controlling the use of HEU targets.

One move in this direction was the award of several multimillion-dollar grants earlier this year, both to McDermott International's Babcock & Wilcox Technical Services Group and a joint venture between General Electric and Hitachi in order to develop LEU-based medical radioisotope production.

Although for such huge organizations, radioisotope production is just a tiny part of their overall businesses, it will be worthwhile keeping an eye on them, as well as institutions such as Missouri University, which runs the Missouri University Research Reactor (MURR). It too is looking at developing Mo-99 LEU-based production capacity, maybe with a pharmaceutical partner. (Babcock & Wilcox is teaming up with Covidien.)

Similarly, since the International Atomic Energy Agency's "Coordinated Research Project (CRP) on Developing Techniques for Small-Scale Indigenous Production of Mo-99 using LEU or Neutron Activation" (which comes to an end this year) is focused on small-scale indigenous production, it will probably be worth keeping up-to-date with just which commercial partners (probably technetium-99m generator producers and distributors) the seven or so "contract holders" in the CRP may be talking to or teaming up with.

 

Conclusion

Stability of supply in the medical radioisotope market is now of overriding importance. Being a stakeholder in any entity that can help provide this stability, particularly in the U.S., could be a very attractive proposition.

 

Resources

American Nuclear Society (ANS)

Australian Nuclear Science and Technology Organisation (ANSTO)

European Nuclear Society (ENS)

International Source Suppliers and Producers Association (ISSPA)

Nuclear Engineering International (NEI)

Radiochemistry Society

The American Association of Physicists in Medicine (AAPM)

The National Academies

U.S. Department of Energy - Office of Health, Safety and Security

United States Nuclear Regulatory Commission (U.S. NRC)

World Nuclear Association (WNA)

 

Endnotes

  1. "In diagnostic nuclear medicine, tracer amounts of a radioactive biologically active substance are administered to a patient. The tracer distribution is subsequently detected and visualised by means of a dedicated radiation detector, such as a gamma camera. The active substance is chosen in such a way that its spatial and temporal distribution in the body reflects a particular body or metabolic function and therefore allows inferring diagnostic information. The substance is labelled with a radionuclide to allow its detection. Only tracers are administered in order not to disturb the body functions. Examples are Tc-99m labelled red blood cells to study heart function, or Tc-99m labeled diphosphonates for visualising bone metabolism." The medical Isotope crisis: The European Nuclear Society
  2. "6-day curies" refers to the number of curies present in a shipment of Mo-99 six days after it leaves a producer's facilities. A curie is a measure of radioactivity and equates to some 37 billion disintegrations per second. In general, in the isotope industry, most producers price their products based on how much radioactivity remains in their products six days after they leave their facilities.

 

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