If you’ve campaigned against the nuclear industry, you’ve probably faced the argument that we need uranium mining and nuclear reactors for the production of medical radioisotopes. Bollocks! Here’s a short summary of the issues.

What is nuclear medicine?

Most nuclear medicine procedures are diagnostic (90% to 99% depending on the country): radioactive substances (radioisotopes) are administered to the patient (usually by injection) and as the radioisotopes ‘decay’ they emit radiation which is captured by a camera and used to generate an image. A small minority (1% to 10%) of nuclear medicine procedures are palliative (pain relieving) or therapeutic.

Where do the radioisotopes come from?

Nearly all medical radioisotopes are produced in nuclear research reactors (about 80%) or in cyclotrons (about 20%). About 75% of all nuclear medicine procedures use the radioisotope technetium-99m (Tc-99m). Most Tc-99m is derived from the parent radioisotope molybdenum-99 (Mo-99) which is currently produced in research reactors. There are several non reactor methods of producing Mo-99/Tc-99m; large scale development of a non reactor technique would dramatically reduce the current reliance on research reactors, but none of these techniques is in routine use.

So we need nuclear research reactors, then?

Well, yes and no. If all reactor production of medical radioisotopes were to stop tomorrow, the world wouldn’t end. We’d still have cyclotron produced radioisotopes, and a plethora of other diagnostic, palliative and therapeutic products and procedures. But a more realistic scenario involves a phased reduction in the use of reactor-produced radioisotopes combined with the further development of alternatives.

What are the alternatives?

There are several, but for the sake of simplicity it’s best to consider two main areas: non reactor methods of producing radioisotopes (especially cyclotrons), and alternative clinical technologies.

CYCLOTRONS beyond to a class of machines called particle accelerators, electromagnetic devices which accelerate charged particles to enormous velocities. The particles can then be directed to hit a target and thus produce radioisotopes. Over 250 cyclotrons are operating around the world.

Because they are powered by electricity rather than the uranium fission reaction of a nuclear reactor, cyclotrons have important advantages:
+ they generate only a tiny fraction of the waste of research reactors (typically less than 10%)
+ they pose no risk in relation to nuclear weapons proliferation (for comparison, consider the use of research reactors to produce plutonium for weapons in India and Israel); and
+ cyclotrons are much safer (for comparison, there have been five fatal research reactor accidents according to the International Atomic Energy Agency).

ALTERNATIVE CLINICAL TECHNOLOGIES competing with nuclear medicine include magnetic resonance imaging, X radiology, computerised tomography and ultrasound. Moreover the competition is not only between imaging techniques; there are also many chemical and biological alternatives to radioisotopes for in vitro studies and research.

Don’t confuse these issues with the debate over electricity sources. They are parallel debates:
+ for electricity: nuclear power versus fossil fuels versus renewables and conservation
+ for medicine and science: nuclear research reactors versus alternative technologies such as cyclotrons and spallation sources.

So do we need a new nuclear research reactor in Australia: at least until the alternatives are further developed?

No. A better strategy would be to close the existing HIFAR reactor at Lucas Heights in southern Sydney combined with:
1. greater reliance on imported radioisotopes;
2. ongoing use of the existing cyclotrons in Sydney and Melbourne and others that are likely to be be built in Australia;
3. further research into advanced, non reactor radioisotope sources such as cyclotrons, with the aim of sharply reducing demand for imported, reactor produced radioisotopes; and
4. greater reliance on alternative clinical technologies (as discussed above).

A couple of important, general points on this strategy:
+ all of the above strategies are based on existing, fully developed, commercialised technologies. So without any technological advancement in any of the four fields listed, the closure of the HIFAR reactor would have negligible impact on the practice of nuclear medicine.
+ none of these four strategies alone would compensate for the closure of HIFAR; but altogether the four pronged strategy is more than adequate. This point needs emphasis because proponents of a new reactor habitually leap from a critique of just one of the four proposed strategies to the false conclusion that a new reactor is required.

But if we IMPORT reactor produced radioisotopes, aren’t we EXPORTING the problems?

Yes. The mix of strategies outlined above would and should change over time. In particular, the reliance on imported reactor produced radioisotopes should be reduced because it leaves other countries to deal with the problems posed by research reactors, not least the legacy of radioactive waste. Properly funded research into alternative radioisotope production technologies (primarily cyclotrons and spallation technology) and alternative clinical technologies will enable reduced reliance on imported reactor produced radioisotopes.

Until then, it’s worth keeping in mind that it’s the fault of governments and the nuclear industry (not anti nuclear campaigners) that reactor technology has received vastly more funding than alternative, safer, cleaner technologies over the past fifty years. Also, to the extent that there is still a requirement for reactor produced radioisotopes, the fewer reactors the better. The argument that each country using reactor produced radioisotopes should operate its own reactor is a recipe for madness.

Whatever the ethical problems with importation, it is certainly a viable alternative to a domestic reactor for numerous important radioisotopes, including the most commonly used diagnostic radioisotope technetium99m (actually it is the longer lived parent radioisotope molybdenum99 that is imported) and also therapeutic and palliative radioisotopes.

The major global radioisotope suppliers have the capacity to supply world demand several times over. More than three quarters of all nuclear medicine procedures carried out around the world use imported radioisotopes. Countries largely reliant on imported radioisotopes include advanced industrial countries such as the United States, Britain, and Japan; in these countries nuclear medicine is widely practised and technically sophisticated despite the heavy reliance on imported radioisotopes.

You might hear the argument that radioisotopes with short half lives could not be imported. True, but almost all of the short lived radioisotopes used in nuclear medicine are produced in cyclotrons, not research reactors. With no research reactor in Australia, over 99% of nuclear medicine procedures would be unaffected, using either cyclotron-produced radioisotopes or imported radioisotopes. As for the small number of rarely used radioisotopes that would not be available, alternative clinical technologies can easily fill this gap.

What about the opportunity costs of building a new reactor?

OK, I know that wasn’t the question on your mind ... but it’s an important and much neglected issue.

A new reactor in Australia would cost at least $300 million, with waste management, reactor decommissioning and other costs adding substantially to the overall cost. There are better ways of spending several hundred million dollars. The medical advantages of building a new reactor are marginal even without consideration of the opportunity costs. The funds could be invested in almost any area of clinical or preventative medicine, public health, or primary health care and yield greater public health benefits than a new reactor. If wisely invested, the funds would be vastly more beneficial to the public health.

Thus Dr. Bill Williams, a Family Physician with 20 years experience, noted in his submission to a Senate Select Committee inquiry in 2000:

"From where I sit gazing at the health horizon across my surgery desk, I see many more promising fields of endeavour where I would like to see my tax dollars being spent in research and development. A few brief examples:
1. Aboriginal health. I have spent much of the past decade working for remote Aboriginal health services in the Northern Territory, where the basics of human wellness are yet to be properly addressed. Clean water, nutritious food, appropriate shelter and adequate sanitation are not scientifically "sexy". But basic research in central Australia has made significant inroads - life-saving inroads - into this truly awful situation.
2. Tobacco control. Cigarette smoking will kill many more Australians than even the most wildly optimistic nuclear scientist could hope to cure through so-far unspecified groundbreaking isotopic inventions. Research into smoking-prevention and cessation will reap far greater life-saving benefits in the short and the longer term."

What about uranium mining?

Research reactors use very little uranium fuel, typically some tens of kilograms annually. Already-mined uranium could supply all the research reactors in the world for hundreds or thousands of years. And remember the aim is to phase out the use of research reactors altogether.

Where can I get more information?

Professor Barry Allen, "Benefits of Nuclear Reactor Still Unclear", Search, Vol.28(9), 1997, p.259.

Transcript of SBS documentary on the reactor/radioisotope debates: <http://www.geocities.com/jimgreen3/sbs.html>

Jim Green, 1997, PhD thesis - "Reactors, Radioisotopes & the HIFAR Controversy", Department of Science and Technology Studies, University of Wollongong.

Nuclear medicine uses radiation to provide diagnostic information about the functioning of a person's specific organs.

Radiotherapy can be used to treat some medical conditions, especially cancer, using radiation to weaken or destroy particular cells.

Millions of nuclear medicine procedures are performed each year, and demand for radioisotopes is increasing rapidly.

NUCLEAR MEDICINE

This is a branch of medicine that uses radiation to provide information about the functioning of a person's specific organs or to treat disease. In most cases, the information is used by physicians to make a quick, accurate diagnosis of the patient's illness. The thyroid, bones, heart, liver and many other organs can be easily imaged, and disorders in their function revealed. In some cases radiation can be used to treat diseased organs, or tumours.

In developed countries (26% of world population) the frequency of diagnostic nuclear medicine is 1.9% per year, and the frequency of therapy with radioisotopes is about one tenth of this.

DIAGNOSIS

Diagnostic techniques in nuclear medicine use radioactive tracers which emit gamma rays from within the body. These tracers are generally short-lived isotopes linked to chemical compounds which permit specific physiological processes to be scrutinised. They can be given by injection, inhalation or orally. The first type are where single photons are detected by a gamma camera which can view organs from many different angles. The camera builds up an image from the points from which radiation is emitted; this image is enhanced by a computer and viewed by a physician on a monitor for indications of abnormal conditions.

A more recent development is Positron Emission Tomography (PET) which is a more precise and sophisticated technique using isotopes produced in a cyclotron. A positron-emitting radionuclide is introduced, usually by injection, and accumulates in the target tissue. As it decays it emits a positron, which promptly combines with a nearby electron resulting in the simultaneous emission of two identifiable gamma rays in opposite directions. These are detected by a PET camera and give very precise indication of their origin. PET's most important clinical role is in oncology, with fluorine-18 as the tracer, since it has proven to be the most accurate non-invasive method of detecting and evaluating most cancers. It is also well used in cardiac and brain imaging.

Positioning of the radiation source within the body makes the fundamental difference between nuclear medicine imaging and other imaging techniques such as x-rays. Gamma imaging by either method described provides a view of the position and concentration of the radioisotope within the body. Organ malfunction can be indicated if the isotope is either partially taken up in the organ (cold spot), or taken up in excess (hot spot). If a series of images is taken over a period of time, an unusual pattern or rate of isotope movement could indicate malfunction in the organ.

A distinct advantage of nuclear imaging over x-ray techniques is that both bone and soft tissue can be imaged very successfully. This has led to its common use in developed countries where the probability of anyone having such a test is about one in two and rising.

The mean effective dose is 4.6 mSv per diagnostic procedure.

RADIOTHERAPY

Rapidly dividing cells are particularly sensitive to damage by radiation. For this reason, some cancerous growths can be controlled or eliminated by irradiating the area containing the growth. External irradiation can be carried out using a gamma beam from a radioactive cobalt-60 source, though in developed countries the much more versatile linear accelerators are now being utilised as a high-energy x-ray source (gamma and x-rays are much the same).

Internal radiotherapy is by administering or planting a small radiation source, usually a gamma or beta emitter, in the target area. Iodine-131 is commonly used to treat thyroid cancer, probably the most successful kind of cancer treatment. Iridium-192 implants are used especially in the head and breast. They are produced in wire form and are introduced through a catheter to the target area. After administering the correct dose, the implant wire is removed to shielded storage. This procedure gives less overall radiation to the body, is more localised to the target tumour and is cost effective.

Treating leukaemia may involve a bone marrow transplant, in which case the defective bone marrow will first be killed off with a massive (and otherwise lethal) dose of radiation before being replaced with healthy bone marrow from a donor.

Many therapeutic procedures are palliative, usually to relieve pain. For instance, strontium-89 and (increasingly) samarium 153 are used for the relief of cancer-induced bone pain.

A new field is targeted alpha therapy (TAT), especially for the control of dispersed cancers. The short range of very energetic alpha emissions in tissue means that a large fraction of that radiative energy goes into the targeted cancer cells, once a carrier has taken the alpha-emitting radionuclide to exactly the right place. Laboratory studies are encouraging and clinical trials for leukaemia, cystic glioma and melanoma are under way.

An experimental development of this is neutron capture therapy using boron-10 which concentrates in malignant brain tumours. The patient is then irradiated with thermal neutrons which are strongly absorbed by the boron, producing high-energy alpha particles which kill the cancer. This requires the patient to be brought to a nuclear reactor, rather than the radioisotopes being taken to the patient.

With any therapeutic procedure the aim is to confine the radiation to well-defined target volumes of the patient. The doses per therapeutic procedure are typically 20-60 Gy.

BIOCHEMICAL ANALYSIS

It is very easy to detect the presence or absence of some radioactive materials even when they exist in very low concentrations. Radioisotopes can therefore be used to label molecules of biological samples in vitro (out of the body). Pathologists have devised hundreds of tests to determine the constituents of blood, serum, urine, hormones, antigens and many drugs by means of associated radioisotopes. These procedures are known as radioimmuno assays and, although the biochemistry is complex, kits manufactured for laboratory use are very easy to use and give accurate results.

DIAGNOSTIC RADIOPHARMACEUTICALS

Every organ in our bodies acts differently from a chemical point of view. Doctors and chemists have identified a number of chemicals which are absorbed by specific organs. The thyroid, for example, takes up iodine, the brain consumes quantities of glucose, and so on. With this knowledge, radiopharmacists are able to attach various radioisotopes to biologically active substances. Once a radioactive form of one of these substances enters the body, it is incorporated into the normal biological processes and excreted in the usual ways.

Diagnostic radiopharmaceuticals can be used to examine blood flow to the brain, functioning of the liver, lungs, heart or kidneys, to assess bone growth, and to confirm other diagnostic procedures. Another important use is to predict the effects of surgery and assess changes since treatment.

The amount of the radiopharmaceutical given to a patient is just sufficient to obtain the required information before its decay. The radiation dose received is medically insignificant. The patient experiences no discomfort during the test and after a short time there is no trace that the test was ever done. The non-invasive nature of this technology, together with the ability to observe an organ functioning from outside the body, makes this technique a powerful diagnostic tool.

A radioisotope used for diagnosis must emit gamma rays of sufficient energy to escape from the body and it must have a half-life short enough for it to decay away soon after imaging is completed.

The radioisotope most widely used in medicine is technetium-99m, , employed in some 80% of all nuclear medicine procedures. It is an isotope of the artificially-produced element technetium and it has almost ideal characteristics for a nuclear medicine scan. These are:
- It has a half-life of six hours which is long enough to examine metabolic processes yet short enough to minimise the radiation dose to the patient.
- Technetium-99m decays by a process called "isomeric"; which emits gamma rays and low energy electrons. Since there is no high energy beta emission the radiation dose to the patient is low.
- The low energy gamma rays it emits easily escape the human body and are accurately detected by a gamma camera. Once again the radiation dose to the patient is minimised.
- The chemistry of technetium is so versatile it can form tracers by being incorporated into a range of biologically-active substances to ensure that it concentrates in the tissue or organ of interest.

Its logistics also favour its use. Technetium generators, a lead pot enclosing a glass tube containing the radioisotope, are supplied to hospitals from the nuclear reactor where the isotopes are made. They contain molybdenum-99, with a half-life of 66 hours, which progressively decays to technetium-99. The Tc-99 is washed out of the lead pot by saline solution when it is required. After two weeks or less the generator is returned for recharging.

Myocardial Perfusion Imaging (MPI) uses thallium-201 chloride or technetium-99m and is important for detection and prognosis of coronary artery disease.

For PET imaging, the main radiopharmaceutical is Fluoro-dioxy glucose (FDG) incorporating F-18, with a half-life of just under two hours, as a tracer.

THERAPEUTIC RADIOPHARMACEUTICALS

For some medical conditions, it is useful to destroy or weaken malfunctioning cells using radiation. The radioisotope that generates the radiation can be localised in the required organ in the same way it is used for diagnosis - through a radioactive element following its usual biological path, or through the element being attached to a suitable biological compound. In most cases, it is beta radiation which causes the destruction of the damaged cells. This is radiotherapy. Short-range radiotherapy is known as brachytherapy. Although radiotherapy is less common than diagnostic use of radioactive material in medicine, it has nevertheless become widespread and important.

Iodine-131 and phosphorus-32 are examples of two radioisotopes used for therapy. Iodine-131 is used to treat the thyroid for cancers and other abnormal conditions such as hyperthyroidism (over-active thyroid). In a disease called Polycythemia vera, an excess of red blood cells is produced in the bone marrow. Phosphorus-32 is used to control this excess.

A new and still experimental procedure uses boron-10 which concentrates in the tumor. The patient is then irradiated with neutrons which are strongly absorbed by the boron, to produce high-energy alpha particles which kill the cancer.

For targeted alpha therapy (TAT), actinium-225 is readily available now, from which the daughter Bi-213 can be obtained to label targeting molecules.

Considerable medical research is being conducted worldwide into the use of radionuclides attached to highly specific biological chemicals such as immunoglobulin molecules (monoclonal antibodies). The eventual tagging of these cells with a therapeutic dose of radiation may lead to the regression - or even cure - of some diseases.

ISOTOPES USED IN MEDICINE

Reactor Radioisotopes

Molybdenum-99: Used as the 'parent' in a generator to produce technetium-99m, the most widely used isotope in nuclear medicine.

Technetium-99m: Used in to image the skeleton and heart muscle in particular, but also for brain, thyroid, lungs (perfusion and ventilation), liver, spleen, kidney (structure and filtration rate), gall bladder, bone marrow, salivary and lacrimal glands, heart blood pool, infection and numerous specialised medical studies.

Chromium-51: Used to label red blood cells and quantify gastro-intestinal protein loss.

Cobalt-60: Used for external beam radiotherapy.

Copper-64: Used to study genetic diseases affecting copper metabolism, such as Wilson's and Menke's diseases.

Dysprosium-165: Used as an aggregated hydroxide for synovectomy treatment of arthritis.

Ytterbium-169: Used for cerebrospinal fluid studies in the brain.

Iodine-125: Used in cancer brachytherapy (prostate and brain), also diagnostically to evaluate the filtration rate of kidneys and to diagnose deep vein thrombosis in the leg. It is also widely used in radioimmuno assays to show the presence of hormones in tiny quantities.

Iodine-131: Widely used in treating thyroid cancer and in imaging the thyroid; also in diagnosis of abnormal liver function, renal (kidney) blood flow and urinary tract obstruction. A strong gamma emitter, but used for beta therapy.

Iridium-192: Supplied in wire form for use as an internal radiotherapy source for cancer treatment.

Iron-59: Used in studies of iron metabolism in the spleen.

Phosphorus-32: Used in the treatment of polycythemia vera (excess red blood cells). Beta emitter.

Potassium-42: Used for the determination of exchangeable potassium in coronary blood flow.

Rhenium-188 (derived from Tungsten-188): Used to beta irradiate coronary arteries from an angioplasty balloon.

Samarium-153: Very effective in relieving the pain of secondary cancers lodged in the bone, sold as Quadramet. Also very effective for prostate and breast cancer. Beta emitter.

Selenium-75: Used in the form of seleno-methionine to study the production of digestive enzymes.

Sodium-24: Used for studies of electrolytes within the body.

Strontium-89: Very effective in reducing the pain of prostate cancer. Beta emitter.

Xenon-133, Xenon-127: Used for pulmonary (lung) ventilation studies.

Yttrium-90: Used for cancer therapy and as silicate colloid for the treatment of arthritis in larger joints. Beta emitter.

Radioisotopes of palladium, caesium, gold and ruthenium are also used in brachytherapy.

Cyclotron Radioisotopes

Gallium-67: Used for tumour imaging and localisation of inflammatory lesions (infections).

Thallium-201: Used for diagnosis of coronary artery disease other heart conditions such as heart muscle death and for location of low-grade lymphomas.

Iodine 123: Increasingly used for diagnosis of thyroid function, it is a gamma emitter without the beta radiation of I-131.

Rubidium-81, Krypton-81m: Krypton-81m gas can yield functional images of pulmonary ventilation, e.g. in asthmatic patients, and for the early diagnosis of diseases and function of the lungs.

Indium-111: Used for brain studies, infection and colon transit studies.

Carbon-11, Nitrogen-13, Oxygen-15, Fluorine-18: These are positron emitters used in PET for studying brain physiology and pathology, in particular for localising epileptic focus, and in dementia, psychiatry and neuropharmacology studies. They also have a significant role in cardiology. F-18 in FDG has become very important in detection of cancers and the monitoring of progress in their treatment, using PET.

What are radioisotopes?

There are 82 stable elements and about 275 isotopes of these elements. When a combination of neutrons and protons, which does not already exist in nature, is produced artificially, the atom will be unstable and is called a radioactive isotope or radioisotope.

Radioisotopes can be manufactured in several ways. The most common is by neutron activation in a nuclear reactor. This involves the capture of a neutron by the nucleus of an atom resulting in an excess of neutrons (neutron rich). Some radioisotopes are manufactured in a cyclotron in which protons are introduced to the nucleus resulting in a deficiency of neutrons (proton rich).

The nucleus of a radioisotope usually becomes stable by emitting an alpha and/or beta particle (or positron). These particles may be accompanied by the emission of energy in the form of electromagnetic radiation known as gamma rays. This process is known as radioactive decay.

Radioactive products which are used in medicine are referred to as radiopharmaceuticals.