ANSTO - Australian Nuclear Science and Technology Organisation
ANZAPNM - Australian and New Zealand Association of Physicians in Nuclear Medicine
ARI - Australian Radioisotopes (ANSTO's isotopes subsidiary)
MRI - magnetic resonance imaging
PET - positron emission tomography

The proposal to build a new nuclear reactor in the Sydney suburb of Lucas Heights has been justified with exaggerated claims about "saving lives" with medical isotopes by ANSTO and the federal government.

The evidence for such claims has been lacking in several important areas. Conversely, there is evidence - both direct and indirect - that nuclear medicine would be effected only marginally in the absence of an Australian reactor:
* the direct evidence includes the three-month maintenance shutdown of the HIFAR reactor from February-May 2000, during which there was very little, if any, disruption to nuclear medicine.
* indirect supporting evidence includes the widespread global trade in medical radioisotopes: over three-quarters of all nuclear medicine procedures around the world use imported isotopes, and many countries also operate cyclotrons. It is difficult to see why a greater reliance on imported reactor-produced radioisotopes, combined with domestic cyclotrons, could not produce a satisfactory outcome in Australia as it does in so many other countries.

There is compelling evidence of a beat-up. ABC Radio National's Background Briefing program (March 29, 1998) stated that the federal government decided to "deliberately overstate" the medical arguments and quoted a senior federal government bureaucrat involved in the reactor process saying: "The government decided to push the whole health line, and that included appealing to the emotion of people - the loss of life, the loss of children's lives ... So it was reduced to one point, and an emotional one at that. The government never tried to argue the science of it, the rationality of it." In short: a beat-up.

Only a small minority of nuclear medicine procedures are for therapeutic purposes; the vast majority are diagnostic procedures which, while important, rarely make the difference between life and death. When asked on ABC JJJ radio in December 1998 if it would be a life threatening situation if Australia did not produce medical isotopes locally, Dr. Geoff Bower, then President of the Australian and New Zealand Association of Physicians in Nuclear Medicine (ANZAPNM), said, "Probably not life threatening. I think that's over-dramatising it and that's what people have done to win an argument. I resist that."

The former head of a nuclear medicine department in a capital city wrote in early 2001: "I do not know exactly why the strategic thinkers within ANSTO pushed the radiopharmaceutical line [to justify a new reactor]. They would have been aware that the case was not entirely solid. However, it would have some universal appeal and could be understood by most lay people and the electorate."

Dr. Barry Allen, former Chief Research Scientist at ANSTO, Fellow in the Department of Pharmacy at the University of Sydney, Head of Biomedical Physics Research at the St. George Cancer Care Centre, and author of over 220 publications, wrote in the October 1997 edition of Search (journal of the Australian and New Zealand Association for the Advancement of Science), "(The new) reactor will be a step into the past ... (It) will comprise mostly imported technology and it may well be the last of its kind ever built. Certainly the $300 million reactor will have little impact on cancer prognosis, the major killer of Australians today. In fact, the cost of replacing the reactor is comparable to the whole wish list that arguably could be written for research facilities by the Australian Science, Technology and Engineering Council (ASTEC)."

Professor Allen says:

"Its reported that if we don't have the reactor people will die because they won't be getting their nuclear medicine isotopes. I think that's rather unlikely. Most of the isotopes can be imported into Australia. Some are being generated on the cyclotron. But on the other hand a lot of people are dying of cancer and we're trying to develop new cancer therapies which use isotopes which emit alpha particles which you cannot get from reactors. And if it comes down to cost-benefit, I think a lot more people will be saved if we can proceed with targetted alpha cancer therapy than being stuck with the reactor when we could in fact have imported those isotopes. ... The question is really what the tax-payer of Australia wants. Do they want new therapies or do they want the reactor to be the centre of all research?"

“The thing that worries me is that a lot of money is being spent on this reactor which will not advance our ability to develop new methods and new techniques. The reactor will continue to product isotopes which we’ve been using in the last 10, 20 years. There are some accelerator sources which could produce different types of isotopes. The type that I’m working with now are called alpha-emitting isotopes and they are really very difficult to produce on a reactor, but they do offer new opportunities and new potential for improved cancer therapy methods. Most of the reactor isotopes are good for diagnosis and imaging but not so good for therapy, so the search is really for improved isotopes which will give better therapeutic results.”

Likewise, the federal Department of the Environment was not prepared to parrot government/ANSTO propaganda about medical isotopes in its 1999 report on ANSTO's Environmental Impact Statement. The Department said that national interest / foreign policy issues form the "cornerstone" of the push for a new reactor. Likewise,  the Department of Foreign Affairs and Trade & Australian Safeguards and Non-Proliferation Office said that the plan for a new reactor is "first and foremost" being driven by a foreign policy agenda. The foreign policy / 'national interest' agenda is discussed in detail in a paper by Jean McSorley which you can find here: <http://www.geocities.com/jimgreen3/mcsorley.html>.

There are three reasons why it would be preferable not to build a new reactor for medical isotope production:

* Nuclear weapons. India and Israel have both used research reactors to produce nuclear weapons. Many other countries have used research reactors and associated technologies (e.g. enrichment, reprocessing facilities) in support of covert nuclear weapons programs. Those issues are discussed in brief in a separate paper (www.geocities.com/jimgreen3/dualuse.html) and in detail in another separate paper (www.geocities.com/jimgreen3/rrweapons.html). It would be preferable to use non-reactor technologies to produce isotopes, and to rely more heavily on medical procedures other than nuclear medicine. Export of non-reactor technologies would be a useful, concrete Australian contribution to international efforts to stem the proliferation of nuclear weapons.

* Safety. According to the Australian Academy of Science and the International Atomic Energy Agency, there have been five fatal research reactor accidents. There have been at least 13 serious accidents involving research reactors around the world according to a US report (Bertini, H.W., et al., 1980, "Descriptions of selected accidents that have occurred at  nuclear reactor facilities" Springfield: NTIS.) Research reactor accidents are discussed in a separate paper (www.geocities.com/jimgreen3/accidents.html)

* Radioactive waste. Much of the radioactive waste - including long-lived intermediate level waste - stored at Lucas Heights is a by-product of isotope production and processing. A 1998 article on the International Atomic Energy Agency’s involvement in research reactor waste management programs states (Ritchie, 1998), “A number of concerns were immediately apparent at the beginning of 1993. Many research reactors were in a crisis situation or rapidly approaching a crisis situation. In every case, this was due to spent fuel storage and management problems and the constraints of national laws. It was clear that the capacity for spent fuel storage had been reached or was close to the limit at many research reactors and there were concerns from a materials science point of view about ageing materials in ageing storage facilities.” As the report notes, the situation was much the same five year later: “More than 550 nuclear research reactors are operating or shutdown around the world. At many of these reactors, spent fuel from their operations is stored, pending decisions on its final disposition. In recent years, problems associated with this spent fuel storage have loomed larger in the international nuclear community. Concerns principally focus on the ageing fuel storage facilities, their life extension, and the ultimate disposal of spent fuel assemblies. At both research and test reactors, spent fuel is being stored for longer periods than originally planned and in larger quantities.” (Iain Ritchie (IAEA Division of Nuclear Fuel Cycle and Waste Technology), "Growing Dimensions - Spent FuelManagement at Research Reactors", IAEA Bulletin, Vol.40, No.1, 1998.)

The following strategy can be proposed should HIFAR be permanently shut-down without replacement:

1. Greater reliance on imported isotopes

plus ...

2. Ongoing use of the existing cyclotrons in Sydney and Melbourne and others that are likely to be built in Australia (e.g.
proposals for small cyclotrons in several other capital cities are at various stages of advancement)

plus ...

3. Further research into advanced, non-reactor isotope sources such as accelerator technology (inc. cyclotrons), with the aim of sharply reducing demand for imported, reactor-produced isotopes

plus ...

4. Greater reliance on alternative medical procedures and products, both for patient procedures (e.g. computerised tomography, magnetic resonance imaging and ultrasound) and for research and in vitro studies (a plethora of chemical and biological alternatives).

Some general points on this strategy:

* All of the above strategies are based on existing, fully-developed, commercialised technologies:
- global trade in medical radioisotopes is well established; already about 20% of the isotopes used in nuclear medicine in Australia are imported;
- there are three cyclotrons producing medical radioisotopes in Australia (as well as other particle accelerators producing radioisotopes for medical research) and about 250 cyclotrons producing medical isotopes around the world;
- the use of radioisotopes in medicine (for imaging, palliation, therapy, research) exists alongside a plethora of alternatives medical products and procedures.

Even without any technological advancement in any of the four fields listed, the closure of the HIFAR reactor would have negligible impact.

* None of the four strategies alone would compensate for the closure of HIFAR; but together the proposed 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.

* The mix of strategies would and should change over time. In particular, the reliance on imported reactor-produced isotopes should be reduced so no country has to deal with the problems posed by research reactor usage, e.g. the radioactive waste legacy. Properly-funded R&D into alternative radioisotope production technologies (primarily particle accelerators including cyclotrons) and alternative medical technologies will enable reduced reliance on imported isotopes.

* The opportunity costs of proceeding with a new reactor need consideration. 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, primary health care etc. and yield greater public health benefits than a new reactor. If wisely invested, the funds would be vastly more beneficial to the public health. The question of opportunity costs was addressed by Dr. Bill Williams, a Family Physician with 20 years experience (submission to 1999-2000 Senate Select Committee inquiry into proposed new reactor, volume 2):

       "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:

       - 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.

       - 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.

       Given budgetary limitations, we should be directing health research dollars to areas that genuinely promise
       an attractive return on our investment."

ANSTO marketed products based on the following radioisotopes as at late 1997: americium-241, barium-139, bromine-82, chromium-51, cobalt-60, copper-64, gadolinium-153, gallium-67, gold-198, indium-111, iodine-125, iodine-131, iodine-123, iridium-192, lanthium-140, manganese-56, mercury-197, mercury-203, phosphorus-32, potassium-42, samarium-153, sodium-24, strontium-90, thallium-201.

ANSTO said in a submission to the Senate inquiry into the contract for a new reactor (2000) that it produces the following radioisotopes (which includes some cyclotron-produced radioisotopes (underlined) and some used for non-medical purposes): gold-198, iodine-123, iodine-125, iodine-131, iridium-192, bromide-82, chromium-51, copper-64, indium-111, manganese-56, mercury-197, mercury-203, Mo-99/Tc-99m, phosphorus-32, potassium-42, samarium-153, sodium-24, gallium-67, thallium-201. Also listed are 'school sources' (americium-241, cobalt-60, strontium-90) and 'scientific and industrial sources' (e.g. americium, caesium, iridium-192, ytterbium-169, gadolinium-153, cobalt-60).

According to ANSTO, its radioisotope subsidiary Australian Radioisotopes (ARI) maintained (as at 1993) a market share of “around 80% overall” for radioisotope products and 95% of the Australian market for Mo-99/Tc-99m generators (usually using Mo-99 from HIFAR but sometimes using imported Mo-99).

In 1991-92, about 55% of ARI's sales were of HIFAR radioisotopes and the rest were sales of products imported by ARI or sales of non-radioisotope products. ANSTO says it "supplies only a small number of cold kits as a service".

ARI also plays a role in the sale of radioisotopes produced by the National Medical Cyclotron in Sydney. According to ANSTO, ARI radioisotope sales are about 80% reactor-produced and 20% cyclotron-produced.

According to ANSTO (submission to Senate inquiry, 2000), ANSTO imports small amounts of Mo-99 on an 'as needed' basis and to the extent that it can obtain 'spot' supplies, and ANSTO also imports small quantities of other isotopes that cannot be produced 'economically', or at all, in HIFAR.

Nycomed Amersham is the only foreign licensed supplier of Mo-99/Tc-99 generators and thus ANSTO/ARI's only competitor in the Australian Mo-99/Tc-99m market. As at April 2000, Nycomed Amersham supplied about seven generators each week, manufactured in the UK, of the total Australian demand of about 100 generators.

Nycomed Amersham’s “Health-Care Price List 1997-98” lists products based on the following radioisotopes: chromium-51, cobalt-57, iron-59, indium-111, iodine-131, iodine-125, phosphorus-32, strontium-89, selenium-75, xenon-133, and yttrium-90. Nycomed Amersham supplies roughly 15-20% of the Australian market. Nycomed Amersham advised in April 2000 that all of these radioisotopes are currently imported, “as well as a few others”.

ANSTO has previously stated that it supplies one or more radiopharmaceutical companies with radioisotopes. Nycomed Amersham said that it does not get any products from ANSTO (personal communication, April 2000.)

ANSTO said in a submission to the Senate inquiry into the contract for a new reactor (2000) that:
* ANSTO supplies product throughout Australia, New Zealand and part of Asia
* in addition, under a contract with SiRTEX Limited, ANSTO manufactures Sirspheres, an yttrium-90 labelled microsphere used for the treatment of secondary liver cancer.

Mallinckrodt supplies Australia with some products manufactured in Europe and North America. According to Mallinckrodt, its supply of the Australian market is roughly equivalent to Nycomed Amersham's (in financial terms), though other commentators suggest Mallinckrodt has a considerably smaller market share than Nycomed Amersham. Certainly the product range is different. Mallinckrodt supplies a range of cold kits for labeling in hospitals with radioisotopes, but its supply of radioisotopes is limited to thallium-201, gallium-67, an indium-111 labelled radiopharmaceutical, and perhaps others.

Syncor Du Pont had an Australian distributor, supplying gallium-67, thallium-201 and various other products. For some years this business appears to have been conducted through an agency or subsidiary operated by Mr. Bill Burch. However, since 1996 or 1997, Syncor Du Pont has operated directly in Australia, and it has taken over the operation of a small radiopharmacy in Sydney, which was previously owned by Nycomed Amersham.

Drawing on available literature, and discussions with the suppliers and with doctors, a rough break-down of Australia’s radiopharmaceutical market in 1998 is as follows:

SUPPLIER                    ANNUAL SALES (PERCENTAGE)
ANSTO/ARI                  ~$12 million (~60-67%)
Nycomed Amersham       ~$ 4 million (~20-22%)
Mallinckrodt                  ~$1-3 million (~5-17%)
Syncor Du Pont              ~~$1 million (~~5-6%)
Total:                            ~$18-20 million (100%)

The above figures include some sales of non-radioactive products, such as “cold kits” which are mixed with radioisotopes prior to patient administration.

Medical radioisotopes used in Australia when HIFAR is operating:
 ~50-70% produced by the HIFAR reactor
 ~15-25% produced by cyclotrons in Australia
 ~10-25% imported radioisotopes (reactor- and cyclotron-produced)

Medical radioisotopes used in Australia when HIFAR is shut down:
 none produced by the HIFAR reactor
 ~15-25% produced by cyclotrons in Australia
 ~75-85% imported radioisotopes (reactor- or cyclotron-produced)

The HIFAR reactor at Lucas Heights was shut down for three months from February-May 2000 for maintenance. During the three-month shutdown, little changed except that ANSTO relied on imports to replace a number of radioisotopes usually produced using HIFAR. Hospitals relied on the usual cyclotron-produced isotopes, the usual imported isotopes, and additional imports.

In a submission to the Senate Select Committee inquiry into the contract for a new reactor (2000), ANSTO said that during extended shutdowns, it attempted to import its requirements of Mo-99, iodine-131, iridium-192 and small quantities of other isotopes (unspecified).

ANSTO's executive director Helen Garnett said “there have already been problems with supply of products from overseas” during the three-month reactor shutdown (letter from Helen Garnett to Sutherland Shire Council, April 7, 2000). However ANSTO scientists with greater familiarity with isotope procurement deny this (personal communications).

The key medical radioisotope is technetium-99m (Tc-99m), used in about 70% of all nuclear medicine procedures. Usually Tc-99m is derived from the longer-lived, reactor-produced parent radioisotope, molybdenum-99 (Mo-99). Most of Australia’s Mo-99/Tc-99m usually comes from the HIFAR reactor. According to an ANSTO scientist (personal communication, April 2000), during the three-month HIFAR reactor shutdown:
* all of Australia’s demand for Mo-99/Tc-99m is being met from imported supplies from South Africa and Canada;
* one stop flights are available from both countries
* supply was reliable
* bulk Mo-99 was imported with Mo/Tc generator manufacture continuing at Lucas Heights with little or no difference to the usual situation of ANSTO supplying ARI with bulk Mo-99.

A number of ANSTO staff members wrote to Sutherland Shire Council on March 3, 2000, saying, inter alia:

“The reactor HIFAR will be shut down from 7 February to 1 May, 2000. ANSTO’s isotope production has suffered no dislocation as a result of the shutdown, since bulk supplies of isotopes are purchased from the big international players in Canada and South Africa. Indeed it is understood that we can purchase bulk supplies of radioactive molybdenum (ANSTO’s major seller in the form of a ‘generator’) from one supplier more cheaply than ANSTO can produce it. If HIFAR was so essential to the supply of isotopes why has there been no effective production dislocation during the shutdown?”

“We understand that ANSTO has been obtaining supplies of samarium from South Africa since the HIFAR shutdown in February with no dislocation, this isotope is usually manufactured by ANSTO. It is further understood that ANSTO has stopped its importation of samarium from South Africa to “prove” the need for a new reactor. If this is the case it would appear that ANSTO is orchestrating its own circumstances to ensure a new reactor.”

When the President of the Australian and New Zealand Association of Physicians in Nuclear Medicine, Dr. Barry Ellison, was asked in July 2000 how doctors coped during the shutdown of the HIFAR reactor from February to May for maintenance, he denied that the reactor had been shut down, insisting that he would surely have known about it. But of course the reactor was shut down for three months, and Barry Ellison wasn’t the only doctor who failed to notice.

Cyclotrons are electromagnetic devices powered by electricity rather than the uranium fission reaction in a nuclear reactor. Cyclotrons thus offer some important advantages:
Radioactive waste: The waste streams from research reactors are proving highly problematic in many countries, as discussed above. Cyclotrons produce only a tiny fraction of the waste stream when compared with reactors ... and no spent fuel whatsoever.
Nuclear weapons: Research reactors (and associated technologies) have been used in many countries in support of nuclear weapons programs, as mentioned above. It would be preferable to use non-reactor technologies to produce isotopes, and to rely more heavily on medical procedures other than reactor-based nuclear medicine. Export of cyclotrons and other non-reactor technologies would be a useful, concrete Australian contribution to international efforts to stem the proliferation of nuclear weapons.
Safety: There have been several fatal research reactor accidents, and numerous serious accidents. No fatal cyclotron accidents have occurred.

20-25% of nuclear medicine procedures in Australia use cyclotron-produced isotopes (many of them produced in cyclotrons in
Sydney and Melbourne), and this proportion has been growing steadily.

There are several reasons for the growing use of particle accelerators (especially cyclotrons) for medical isotope production, in particular growing interest in procuring functional, biochemical information. Technical advances have expanded the range of isotopes that can be produced with accelerators, and they have enabled more efficient, reliable, and economical production. Technical advances have included:
* the development of high-power cyclotrons with two or more beams allowing simultaneous bombardment of several targets;
* the development of more compact and less expensive cyclotrons and linacs, with power levels of 3-10 MeV, for
hospital-based production of isotopes used in positron emission tomography;
* improvements in target design and in the availability of isotopically-enriched target materials; and
* the flexibility of configuration of medical cyclotrons and thus the flexibility of operation and the range of applications.

ANSTO acknowledges that the "cutting edge" of nuclear medicine involves the use of cyclotron-produced isotopes. The Australian and New Zealand Association of Physicians in Nuclear Medicine says "many of the reactor-produced isotopes have been made in cyclotrons". ANSTO's Chief Executive, Professor Garnett, says "you can put target A in the reactor and get the product out and put target B in a cyclotron and get the same product out".

About 250 cyclotrons are in use for isotope production in about 34 countries. Several dozen of these cyclotrons are
operated by radiopharmaceutical companies and are dedicated to isotope production.

Australia has three cyclotrons - the National Medical Cyclotron in Sydney, and two cyclotrons in Melbourne dedicated to producing short-lived radioisotopes for positron emission tomography.

There are several examples of useful radioisotopes now produced in cyclotrons which used to be produced only in reactors. A recent example is palladium-103, a cancer therapeutic. Reactor supply dried up, so scientists in the United States took up the challenge and successfully developed a cyclotron method to produce palladium-103.

Developing and implementing an accelerator/cyclotron method of producing Mo-99/Tc-99m is a key issue because Tc-99m is used in most nuclear medicine studies; this issue is discussed in a report by US experts commissioned by the Sutherland Shire Council. <www.geocities.com/jimgreen3/medicine5.html>

IMPORTATION: INTERNATIONAL CONTEXT

Several global radiopharmaceutical companies have invested tens of millions of dollars in reactors and isotope processing facilities in the past decade. These companies include MDS Nordion, Mallinckrodt, Nycomed Amersham, and the Nuclear Energy Corporation of South Africa. Two reactors in Canada alone have the capacity to produce more than 100% of the world's demand for several medical isotopes, including the “workhorse” of nuclear medicine, molybdenum-99/technetium-99m, as well as iodine-131 and iodine-125. Two new “Maple” reactors in Canada will ensure that MDS Nordion maintains its dominant position in the global market. The major global suppliers have the capacity to supply world demand several times over.

The supply chains, technologies (e.g shielding), and regulatory apparatus for international isotope trade are in place. Several organisations around the world have experience and expertise in the establishment of long supply lines. For example, MDS Nordion's isotopes are used in over 60 countries, over 18 million patient procedures are carried out using MDS Nordion’s isotopes annually, MDS Nordion isotopes produced in Canada are delivered to and used in 1300 centres in Japan and 5000 centres in the USA, and MDS Nordion ships isotopes almost every day to the USA, Europe, Japan and elsewhere. (Speech by John Morrison, President & CEO, MDS Nordion, to the Canadian Nuclear Association 39th Annual Conference & The Canadian Nuclear Society 20th Annual Conference, Montreal, May 31, 1999, <www.mds.nordion.com>.)

More than three quarters of all nuclear medicine procedures carried out around the world use imported isotopes. Countries largely reliant on imported isotopes include advanced industrial countries such as the US, the UK, and Japan. Together these three countries account for over two thirds of world usage of medical isotopes. There is no indication that delayed or failed delivery is common in these countries. Expressions of concern about reliability of supply are rarely if ever found in the American or European professional literature and senior personnel involved in radiopharmaceutical supply in Japan tell me that supply of Mo-99 from Canada is regular, and that in the (unlikely) event of supply from Canada drying up, they would prefer to find alternative overseas suppliers rather than using domestic research reactors (which are primarily used for scientific research including research in support of nuclear power).

Vertical integration of the industry - which involves radiopharmaceutical companies moving “upstream” into bulk radioisotope production and also “downstream” into processing functions previously carried out in hospital radiopharmacies - has improved (and is likely to continue to improve) reliability of supply by streamlining regimes of production, processing, and distribution. For example, the Nuclear Energy Corporation of South Africa operates a fully-integrated operation for the production of Mo-99 which is exported to several countries including Australia.

Most of the radioisotopes used throughout the world are imported from other countries. For example the US, Japan, and the UK all rely heavily on imported radioisotopes. Together these three countries account for over two thirds of world usage of medical radioisotopes. There is no indication that delayed or failed delivery is common in these countries. Expressions of concern about reliability of supply are rarely if ever found in the American or European professional literature.

IMPORTATION: AUSTRALIA

Given the overseas experience, it is difficult to see why a greater reliance on imported radioisotopes is regarded as a problematic option in Australia.

ANSTO acknowledges that "it is possible to import many isotopes". In the absence of a domestic reactor, Australian doctors would still have access to the four isotopes - technetium-99m, gallium-67, thallium-201, and iodine-131 - which account for over 95% of nuclear medicine procedures, and doctors would also have access to literally dozens of other isotopes, whether imported or produced in domestic cyclotrons.

In ANSTO’s Draft EIS on the proposed new reactor (p.6-11--6-13), the following isotopes are listed in the column
“importation for routine clinical use possible”: chromium-51, cobalt-60, erbium-169, indium-111, iodine-125, iodine-131, iridium-192, lutenium-177, Mo-99, paladium-103, phosphorus-32, rhenium-188, selenium-75, strontium-89, tantalum-182, thallium-201, tin-117m, tungsten-188, xenon-133, yttrium-90, and lastly, yttrium-91 is listed as a “maybe” for importation for routine clinical use.

A submission to the 1993 Research Reactor Review listed the following isotopes, which had been imported into Australia: americium-241, curium-244, cadmium-109, plutonium-238, caesium-137, hydrogen-3, selenium-75, calcium-45, iron-59, iodine-12, californium-252, phosphorus-32, gallium-67, indium-111, thallium-201, xenon-133, chromium-51, and yttrium-90.

Nycomed Amersham’s “Health-Care Price List 1997-98” lists products based on the following isotopes: chromium-51,
cobalt-57, iron-59, indium-111, iodine-131, iodine-125, phosphorus-32, strontium-89, selenium-75, xenon-133, and
yttrium-90. Nycomed Amersham advised in April 2000 that all of the isotopes listed in the 1997-98 Price List are currently imported, “as well as a few others”.

Another argument is that because of the relatively small size of the Australian market, suppliers would be likely to interrupt Australian supply in the case of shortages rather than disrupt supply to the larger, more lucrative markets. This is speculation at best. The Research Reactor Review (1993, p.94) noted that there was no evidence of this having happened. Moreover this argument assumes shortages of supply which are unlikely to occur given the investments of the major radiopharmaceutical companies in recent years.

Ongoing research into parent-daughter generator systems promises to further increase the international trade in isotopes and lessen the need for domestic reactors and accelerators. The parent isotopes have half lives which allow for long-distance transport in most cases.

ANSTO says that its same-day or next-day delivery service, particularly important for urgent medical procedures, would be difficult to maintain in the absence of a reactor. This problem certainly would be encountered, but it would apply only to some infrequently-used, short-lived, reactor-produced radioisotopes.

Concerns have been expressed in recent years (e.g. by the Association of Physicians in Nuclear Medicine) about restrictions on the maximum amount of radioactivity that can be imported legally and safely. The maximum radioactivity allowed on an aircraft is known as the Transportation Index or TI. Other countries import large quantities of radioisotopes - for example the USA and Japan have relied on Canada for their entire supply of Mo-99 (far greater than Australian demand) for some years - and have clearly found a way around the TI problem or found it not to be a problem in the first place. TIs for Mo/Tc generators vary depending on the shielding. For example small Nycomed Amersham generators are shielded with lead and the TI ranges from 0.8 to 3.4. Larger generators are shielded with depleted uranium (DU) and the TIs are much lower (despite the enclosed radioactivity being higher), ranging from 0.8 to 1.2. I do not know what shielding is used for bulk Mo-99 supplies but suspect that DU is used. (Bulk Mo-99 can be used for generators or for direct production of Tc-99m radiopharmaceuticals.)

IMPORTATION: ETHICS

The only serious problem with greater reliance on imported reactor isotopes concerns the ethics of relying on other countries to operate reactors and to deal with the problems such as radioactive waste. It would be preferable to rely completely on advanced isotope sources - such as cyclotrons and spallation sources - rather than nuclear reactors. The reliance on reactors - wherever located - should be wound back through greater R&D into non-reactor production technologies and greater use of the plethora of clinical technologies which compete with reactor-dependent nuclear medicine.

Helen Garnett, ANSTO’s executive director (letter to the Mayor of the Sutherland Shire, April 7, 2000), said that apart from the practical difficulties posed by importation of radioisotopes, “it is morally dubious to say that we are not prepared, as a community, to accept the impacts, however small they may be, of new and advanced technologies such as the replacement research reactor, but we are perfectly willing to accept the undoubted benefits by importing the products from overseas with the overseas community accepting those impacts. By way of example, the need to ship greater quantities of each isotope to compensate for decay in transit to Australia, would mean that the production of radioactive wastes would be greater in the country of origin.” Garnett’s comments raise the following issues:
* ANSTO routinely imports radioisotopes and appears not to be concerned by the moral issues posed by this routine importation;
* if HIFAR were to be shut down without replacement, reliance on imported radioisotopes could be reduced by developing accelerator and/or spallation methods to produce key radioisotopes such as Mo-99/Tc-99. ANSTO could engage itself in research to that end, but has never done so.
* the total waste legacy of a small number of research reactors producing most of the radioisotopes used internationally (as is the current practice) is certain to be less than would be the case if each country supplied domestic demand with domestic reactors. This applies regardless of radioactive decay in-transit.
* ANSTO does not consider it “morally dubious” to ask other countries (specifically, France) to accept the impact of reprocessing ANSTO’s spent fuel. In contrast, the Research Reactor Review (1993, p.212) said, in relation to overseas reprocessing, that “exporting an Australian problem is morally dubious.”

Evidence given by a nuclear medicine specialist, Dr. Harvey Turner, to the 1993 Research Reactor Review, pointed to non-medical aspects of the isotope market in Australia. Turner said that, in Western Australia, there was strong competition between ANSTO and foreign suppliers for supply of a number of isotopes. According to Turner, the Australian products were of inferior quality. Turner said that: “Western Australia, for purely chauvinistic reasons, elected to go with the ANSTO product, because there was a threat that, if they did not have a market, they would close down their production facility for isotopes in Australia. ... In fact, the multi-national companies were considering legal action under the Trade Practices Act, because they considered that what we were doing was not in the interest of freedom of trade and, indeed, I guess it was not”.(Research Reactor Review, Transcript of Proceedings, Public Hearing, Perth, 23 March 1999, p.780.)

The admission that patients were given ANSTO’s inferior products for “purely chauvinistic reasons” is alarming. In October 1999, ANSTO was asked to investigate Dr. Turner’s statements, but ANSTO has not done so. ANSTO’s radiopharmaceuticals director Stuart Carr said in October 1999 that hospitals convene specialist committees to determine isotope supply arrangements - which is no comfort since presumably it was a specialist committee which decided that patients should be given inferior products for “purely chauvinistic reasons”.

IMPORTATION: MOLYBDENUM-99/TECHNETIUM-99m

The key medical radioisotope is technetium-99m (Tc-99m), used in about 70% of all nuclear medicine procedures. Usually Tc-99m is derived from the longer-lived, reactor-produced parent radioisotope, molybdenum-99 (Mo-99). Most of Australia’s Mo-99/Tc-99m usually comes from the HIFAR reactor. According to an ANSTO scientist (personal communication, April 2000), during the three-month HIFAR reactor shutdown: all of Australia’s demand for Mo-99/Tc-99m was met from imported supplies from South Africa and Canada; one stop flights are available from both countries; supply was reliable; and bulk Mo-99 was imported with generator manufacture continuing at Lucas Heights with little or no difference to the usual situation of ANSTO supplying ARI with bulk Mo-99. Hospitals received the ANSTO Mo/Tc generators as usual, albeit with imported Mo-99. Many doctors were unaware of the closure of the HIFAR reactor.

ANSTO confirms that “When Mo-99 is imported by ANSTO it is in bulk form.” (personal communication, April 18, 2000.)

According to two ANSTO scientists (personal communications, 1999-2000), even when HIFAR is operating, ANSTO has been importing Mo-99 from the Nuclear Energy Corporation of South Africa (NECSA) on a regular or semi-regular basis, the South African Mo-99 is of superior quality to that produced by ANSTO, it is cheaper and delivery from South Africa (via Perth) has been extremely reliable. ANSTO management has not challenged NECSA's claim that less than 0.5% of all its overseas shipments are delayed (NECSA, 1997, personal communication).

ANSTO (submission to Senate inquiry, 2000) has confirmed that it imports small amounts of Mo-99 on an 'as needed' basis, and to the extent that it can obtain 'spot' supplies, from "a number of suppliers" including NECSA even when HIFAR is operating. (Note the acknowledgement that a "number" of suppliers can supply Australia with Mo-99.)

South African Airways (personal communication, April 2000) provided some general information on its activities: “South African Airways flies to Sydney via Perth. We have four flights per week and all flying via Perth. South African Airways does transport radiopharmaceuticals.” If Australia were to rely on South Africa and South Africa alone for supply of bulk Mo-99, it is likely that two or three shipments per week would be required. This could be accommodated within South African Airways schedule of four flights to Sydney each week.

The option of importing Mo-99 to meet most or all of Australia’s requirement has been discussed by Nycomed Amersham (Research Reactor Review submission, 1993): “The Australian requirement for Mo-99 is a relatively small proportion of the world consumption and it would be possible to integrate this isotope volume requirement with that of Amersham's current take-up for its worldwide operations. The isotope has a 3-day half life and this is not foreseen as a particularly onerous aspect for delivery schedules of 3-4 times per week. ... The advantages of bulk purchases and overhead cost recovery of a larger volume are clear. ... The process costs and, in particular, the high cost of waste disposal for this extremely radioactive process (producing Mo-99 via reactor irradiation of enriched uranium targets) could be avoided within ANSTO by delivering the radiochemical in its intermediate form. Such a delivery chain would allow the production of sales of Technetium generators to be continued unaffected.”

ANSTO claims that Tc-99m cannot be imported because of its 6-hour half life. However it is deceit - or in the words of a former ANSTO employee "a public and unnecessary blunder" - to make such a claim without going on to note that the parent isotope, Mo-99, is widely transported all around the world and is imported into Australia on a weekly basis.

The plan to use a refurbished reactor at the Sandia laboratory in the USA for Mo-99 production has been scrapped because of the availability of overseas supplies from several sources.

IMPORTATION: RELIABILITY OF SUPPLY OF RADIOISOTOPES

ANSTO argues against greater reliance on imported isotopes, claiming that “every third isotope shipment is delayed by at least 24 hours”.  (ANSTO, A Replacement Research Reactor for Australia: Q&A, <www.ansto.gov.au/info/cnrr001.html>.)

ANSTO’s claim must be queried on the following grounds:
* ANSTO has refused repeated requests over several years to provide evidence to substantiate its claims about the unreliability of imported radioisotopes. Evidence would surely be presented if such existed.
* current and former ANSTO employees dispute the claim (personal communications 1997-2000; see also the statements by Professor Barry Allen, former ANSTO Chief Research Scientist, in evidence to Senate Economics References Committee (Nuclear Reactor Inquiry) and also Prof. Allen’s comments on ABC Radio National’s Background Briefing program, March 29, 1998, <www.abc.net.au/rn/talks/bbing/bb980329.htm>; and
* radiopharmaceutical companies involved in importing radioisotopes into Australia dispute the claim (personal communications, 1997-2000).
* according to the Nuclear Energy Corporation of South Africa, one of ANSTO's suppliers, the frequency of transport delays from NECSA to its customers is less than 0.5% of all shipments, and the delay is usually less than 30 hours (personal communication, 1997). ANSTO does not dispute NECSA's claim.
* an MDS Nordion Vice-President said in 1999, “we are proud that our record in delivering our medical radioisotope shipments on time around the world exceeds 98%”. (Speech to Canadian Nuclear Association, 1999).
* other distributors such as Nycomed Amersham also claim a high level of reliability.

The 1993 Research Reactor Review report, which in fact said (p.95, 224) that countries importing radioisotopes had either overcome logistical problems, or did not have problems in the first place.

Qantas Data

To provide some concrete data on the reliability of international flights into Australia, data on the arrival times of Qantas flights into Sydney International Airport was monitored for 14 days, from March 20 to April 2. The results are as follows:
* total 336 flights
* 327 flights (97.3%) ahead of schedule, on time or less than 2 hours behind schedule
* 2 flights (0.6%) 2-3 hours late
* 5 flights (1.5%) over 3 hours late
* 2 flights (0.6%) cancelled (no reason given on Qantas website)

Notes on the Qantas data:
* The data was obtained from the Qantas web-site, <www.qantas.com.au>.
* The Qantas web-site does not distinguish direct flights from those which involve one or more stop-overs (except stop-overs in Australia), e.g. for refuelling or passenger pick-up, so it has not been possible to calculate the effect of stop-overs on arrival times in Sydney.
* It is not known which airlines ANSTO uses to import medical radioisotopes. ANSTO says it does not choose the airline - this is a matter for the overseas supplier. Qantas (personal communication, April 2000) says that it regularly imports and exports radiopharmaceuticals; the exports are presumably ANSTO products. Nycomed Amersham uses British Airways, but the British Airways website does not provide information comparing expected and actual arrival times.)
* Some flights involved a stop-over in Australia and these flights are identified on the Qantas web-site. Only flights which arrived in Sydney directly from an overseas destination are included in the above figures. Flights arriving from an overseas destination via an Australian stop-over were monitored from March 27 to April 2. Of a total of 51 flights, 50 arrived ahead of schedule, on time or less than 1 hour behind schedule, and one flight was 1-2 hours late.

In the event that the HIFAR reactor is shut down without replacement, Mo-99 would be imported until an accelerator or spallation method (or methods) of Mo-99/Tc-99m production is fully developed. Cyclotron-produced radioisotopes - which account for 15-25% of nuclear medicine procedures - will of course be available in the absence of a domestic reactor. Mo-99/Tc-99m plus cyclotron-produced radioisotopes account for 90-95% of all nuclear medicine procedures. Several dozen radiopharmaceuticals account for the remaining 5-10% of nuclear medicine procedures, and a large majority of these radiopharmaceuticals will be available even in the absence of a reactor in Australia.

ANSTO and some other proponents of a new reactor claim that in the absence of a domestic reactor, short-lived reactor-produced radioisotopes would no longer be available in Australia. (The half life below which importation is impossible or impractical depends on a number of variables such as the type and proposed application of the radioisotope, and the distance/proximity of the overseas supplier. ANSTO (1997) suggests that radioisotopes with half lives below “about 36 hours” could not be imported.) However, a large majority of the reactor-produced radioisotopes used in nuclear medicine have half lives sufficient for importation. Further, many of the short-lived radioisotopes used in nuclear medicine are cyclotron produced.

Complaints about unavailability of radioisotopes in the absence of a domestic reactor tend to be non-specific. Therefore assessments as to which radioisotopes are the most important are useful. According to Nycomed Amersham (1993 RRR Submission), the most important medical radioisotopes are Mo-99/Tc-99m, iodine-125, iridium-192, iodine-131, chromium-51, and yttrium-90. According to Dr. John Morris (1993 RRR Submission), a (retired) nuclear medicine professional, the five most important radioisotopes are Mo-99/Tc-99m, thallium-201, gallium-67, fluorine-18, and iodine-131, with the next most important being iodine-123 and indium-111.

There should be no problems with supply of any of these radioisotopes in the absence of a domestic reactor - they can all be imported and/or produced in domestic cyclotrons:

Mo-99 would be imported until an accelerator or spallation method (or methods) of Mo-99/Tc-99m production is fully developed. Several producers could supply Australia with bulk Mo-99 (as during HIFAR shutdowns, with generator manufacture at Lucas Heights and an alternative option of production of unit-dose Tc-99m-based radiopharmaceuticals from bulk Mo-99 supplies) - Nycomed Amersham supplies a number of Mo-99/Tc-99m generators to Australia each week from Europe - ANSTO’s EIS (pp.6-11--6-13) lists Mo-99 in its “importation for routine clinical use possible” column.

Iodine-125 - reactor or cyclotron produced - half life 60 days (ample for importation) - research and clinical applications such as radioimmunoassay, kidney studies - some imported, also produced by the National Medical Cyclotron - Nycomed Amersham (1993 RRR Submission) says there would be no difficulty supplying I-125 in research and clinical grades from reactors in the Pacific Basin. Relatively small cyclotrons currently being used for PET radioisotope production can be used to produce iodine-125 (Carrol-Ramsey Associates, January 2000, personal communication.)

Iridium-192 - reactor produced - half life 72 days (ample for importation) - radiographic cancer treatment - Nycomed Amersham (1993 RRR Submission) claims to be the largest consumer of bulk Ir-192 in the world and could supply high-quality Ir-192 sufficient to meet Australian demand - several bulk producers, e.g. in Russia, Sweden, the US (Isotec).

Iodine-131 - reactor produced - the most important therapeutic radioisotope - half life 8 days (ample for importation) - numerous applications in imaging and treatment - both fission-product and irradiation-generated iodine-131 will be available in large quantities around the world for the foreseeable future according to Nycomed Amersham (1993 RRR Submission).

Chromium-51 - reactor produced - half life 28 days (ample for importation) - imaging (e.g. kidney) - produced in about 9 reactors around the world - already imported.

Yttrium-90 - reactor produced - half life 64 hours (sufficient for importation) - treatment of cancer and arthritis - already imported because of patent restrictions - generator system under development using the parent strontium-90 which has a half life of 29 years (Kodina et al., 1997).

Thallium-201, gallium-67, fluorine-18, iodine-123, indium-111 - all cyclotron produced - all can be produced using cyclotrons and/or imported.

ANSTO’s Draft EIS on the proposed new reactor (p.5-15) says the “most significant” radioisotopes produced with a new reactor would be Mo-99, I-131, Ir-192, ytterbium-169, cobalt-60, phosphorus-32, samarium-153, gold-198. To take each in turn:

Mo-99/Tc-99m - see above.

Iodine-131 - see above.

Iridium-192 - see above.

Cobalt-60 - reactor produced - half life 5 years (ample for importation) - radiotherapy - produced in about 15 research reactors around the world and some power reactors.

Yterbbium-169 - half life 32 days (ample for importation) - according to ANSTO, ytterbium-169 has "limited application in industrial radiography". That being the case, one wonders why it is on ANSTO's list of “most significant” radioisotopes to be produced in a new reactor. In any case, yterbbium-169 needs no further consideration here since the focus is on medical radioisotopes.

Phosphorus-32 - half life 14 days (ample for importation) - treatment - already imported. For bone cancer palliation, phosphorus-32 is just one of a number of radioisotopes used. See Ben-Josef and Porter, 1997.

Samarium-153 - Nycomed Amersham said in its Research Reactor Review Submission that “possible supply solutions could be found using Pacific Basin or European reactors as appropriate” for rhenium-186 and samarium-153. ANSTO hopes to export samarium-153 (and may already have done so), so importing it must be an option despite its short half life of 47 hours. There have been unconfirmed reports furing the February-May 2000 HIFAR shutdown that Sa-153 has been obtained from South Africa. Samarium-153 is just one of a number of radioisotopes with applications in bone cancer therapy or palliation - these include strontium-89, phosphorus-32, and rhenium-186. See Ben-Josef and Porter, 1997. See also discussion paper at <www.geocities.com/jimgreen3/samarium.html>

Gold-198 - could this not be imported given the 55 hour half life? Is an accelerator and/or spallation production method theoretically or practically possible? What is this product used for - and how frequently? What alternatives are available?

Some other radioisotopes which have medical uses but have not yet been mentioned are as follows:

Xenon-133 - reactor produced - half life 53 days (ample for importation) - inhalation and blood flow studies - already imported.

Strontium-89 - reactor produced - half life 50 days (ample for importation) - palliation/treatment - already imported.

Iron-59 - reactor produced - half life 45 days (ample for importation) - iron metabolism - already imported.

Selenium-75 - reactor produced - half life 120 days (ample for importation) - pancreatic imaging - already imported.

According to the October 1998 report to Sutherland Shire Council by Applied Economics Pty Ltd (p.11), Nycomed Amersham says it imports californium-252 (half life 2.63 years) and gallium (half life 78.3 hours) although the ANSTO EIS (pp.6-11--6-12) says that these radioisotopes cannot be imported.

A small number of medical radioisotopes would not be available in the absence of a reactor in Australia - radioisotopes which cannot be produced in accelerators (or for which no accelerator method has yet been developed) and which have half lives too short for importation.

According to ANSTO (1997, personal communication), the following radioisotopes would not be available in the absence of a domestic reactor:

• Yttrium-90. However this has been imported into Australia. Moreover a generator system is under development using the long-lived parent radioisotope strontium-90 (Kodina et al., 1997). ANSTO’s Draft EIS on the proposed new reactor (p.6-13) says carrier-free yttrium could be obtained from a generator using fission products extracted from spent fuel.
• Samarium-153. See above - it is not clear that Sa-153 could not be obtained from overseas reactors, nor is there clear evidence that ANSTO’s Sa-153-based Quadramet is superior to a range of alternative treatments for the alleviation of pain associated with (secondary) bone cancer.
• Bromine-82 (half life 35 hours), sodium-24 and copper-64. Demand for these radioisotopes is “very small” according to ANSTO (1997, personal communication). Alternative radioisotopes (or non-radioisotope procedures) can be used for some (perhaps all) of the clinical procedures using these radioisotopes.

Yterbbium-169 - see above.

ANSTO’s Draft EIS on the proposed new reactor (p.6-11--6-13) contains a table which lists a large number of radioisotopes and comments on whether they can be produced by HIFAR, the planned new reactor, cyclotrons, or whether they can be imported. (The list does not include radioisotopes produced, or capable of being produced, using spallation sources.) Now to comment on those radioisotopes which, according to the ANSTO table, could be produced by a new reactor but could not be obtained from cyclotrons or importation:

Samarium-153 - see above.

Gold-198 - see above.

Gold-199 - why could this not be imported given the 74 hour half life?

Bromine-82 and sodium-24 - see above.

Dysprosium-165 - treatment/palliation of arthritis - almost reached the stage of general marketing release as at 1993 (RHB, RRR Submission) - half life 140 mins. What alternative treatments are available and how do they compare with dysprosium-165? What level of usage occurs and what level is expected?

Holmium-166 - a dysprosium-166/holmium-166 generator is under development (and may already be available). See Knapp and Mirzadeh, 1994.

Rhenium-186 - why can this not be imported given the 90.6 hour half life? For the palliation of skeletal metastases, rhenium-186 is but one of a number of radioisotopes used and there are non-radioisotope options available also. Nycomed Amersham (1993 RRR Submission) says possible supply solutions could be found for rhenium-186 and samarium-153, using Pacific Basin or European reactors.

Scandium-47 - why can't this be imported given the 81.6 hour half life? What is it used for? What alternative products/treatments are available?

Conclusion

On the basis of the above information, the only medical radioisotopes for which there is general agreement that supply would not be possible in the absence of an Australian reactor are:
* bromine-82 - half life 35 hours - possibility of importation?
* sodium-24 - half life 14.9 hours
* dysprosium-165 - half life 140 minutes

Only the first two (bromine-82 and sodium-24) were produced by ANSTO as at late 1997. None of these three radioisotopes is listed among the “most significant” radioisotopes which ANSTO/ARI plans to produce with a new reactor (Draft EIS, p.5-15).

In sum, in the absence of a reactor, several dozen radioisotopes would be available, and very few would not. Given that Mo-99/Tc-99m (70-75% of nuclear medicine procedures) and cyclotron-produced radioisotopes (15-25%) would be available, it can be safely assumed that less than 5% of nuclear medicine procedures would be affected by the closure and non-replacement of HIFAR, and it is more likely that the figure is less than 2%, perhaps less than 1%.

For those radioisotopes which would not be available in the absence of a reactor in Australia, there are several options:
* use alternative radioisotopes
* use non-nuclear medical products/procedures
* for some radioisotopes, it may be possible to develop and implement production using accelerators (several are in operation in Australia) or spallation sources (none exist in Australia).

At present, therapeutic or palliative applications account for a very small percentage of nuclear medicine procedures, likely to range from 1-10% depending on the country.

It is possible that new therapeutic radiopharmaceuticals will be developed, but this is by no means certain. For example a study by Frost and Sullivan (1998) stated that, “Although a large number of therapy trials using radioisotopes are in progress, the nuclear therapy modality is in its developing stages. In fact, only four therapeutic radioisotopes for four diseases have received FDA approval and are currently used in the United States.” The Frost and Sullivan study said that only iodine-131-based thyroid cancer radiopharmaceuticals have experienced “unqualified success” and that the US nuclear therapy market has been “very sluggish in recent years as market penetration expectations were not realized.”

A study of therapeutic radioisotope usage in the UK in 1995 found that in terms of administered radioactivity, over 90% was iodine-131 (Clarke et al., 1999). Iodine-131 will be available in large quantities around the world for the foreseeable future according to Nycomed Amersham (1993 Research Reactor Review Submission).

Even if a new range of therapeutic applications for radioisotopes are developed, most of them will be available in Australia even without a domestic reactor for research or production. Some - such as iodine-131 - have half lives of sufficient length to allow importation. Parent/daughter generator systems may allow ongoing supply of other therapeutic radioisotopes under development, without the need for a domestic reactor; examples include tungsten-188/rhenium-188 generators (Hsieh et al., 1997; Hashimoto, 1997), dysprosium-166/holmium-166 generators (Knapp and Mirzadeh, 1994) and strontium-90/yttrium-90 generators (Kodina et al., 1997).

Most therapeutic/palliative radioisotopes under investigation are reactor-produced, but others are accelerator produced. For example, therapeutic cancer applications may be developed for terbium-149, a radioisotope which has been produced in useful quantities in Australia using a tandem accelerator (Sarkar et al., 1997; Imam et al., 1997). Professor Barry Allen (1998, 1998B), former Chief Research Scientist at ANSTO, provides further examples: an accelerator concept for Boron Neutron Capture Therapy (BNCT) under development as an alternative to reactor-based BNCT; and the ability to use accelerator-based spallation techniques to produce therapeutic or palliative radioisotopes similar to those produced in reactors.

Professor Allen also refers to the “rapidly increasing” use of accelerator produced palladium-103 in the USA for prostate cancer therapy. This radioisotope used to be produced exclusively in reactors. Enrichment of the target radioisotope (palladium-102) was dependent on facilities used primarily in support of the US nuclear weapons program. With the closure of a number of those enrichment facilities, Theragenics Corporation developed a cyclotron-based production technique (using a different target material) to supplement reactor-produced palladium-103. Sales have grown to such an extent that Theragenics Corporation expects to have 14 cyclotrons on-line by the end of the year 2000, with eventual plans for a total of 24 cyclotrons. (Carrol-Ramsey Associates, January 2000, personal communication.)

A cyclotron method to produce iodine-125 (used to treat prostate cancer) has also been developed; relatively small cyclotrons currently being used for PET radioisotope production can be used (Carrol-Ramsey Associates, January 2000, personal communication.)

According to McCarthy and Welch (1998), writing in Seminars in Nuclear Medicine, “It is clear that large quantities of various medium to long half lived nuclides can be produced on small biomedical cyclotrons. ... It is highly likely that these medium half-life nuclides will not only be used for therapy, but for the quantitative estimate of dosimetry prior to therapy”.

Technical advances with cyclotron technology were necessary to enable cyclotron production of palladium-103, and further innovations are under investigation to enable production of other therapeutic radioisotopes (Jongen, 1999).

ANSTO said in a submission to the Senate inquiry into the contract for a new reactor (2000) that HIFAR is used to produce the following therapeutic radioisotopes: iodine-131, samarium-153, yttrium-90, iridium-192, gold-198, holmium-166, lutenium-177 and copper-64. ANSTO also said that a number of isotopes not currently produced in HIFAR could be produced in the replacement reactor such as tin-117m, rhenium-186, rhenium-188 and greater quantities of lutenium-177.

Samarium-153

A samarium-153-based radiopharmaceutical (produced and marketed by ANSTO as Quadramet) is sometimes used to alleviate the pain associated with secondary bone cancer. In the absence of a domestic reactor:
* Quadramet can be imported
* alternative products can be used (as they most often are even where Quadramet is available).

A number of ANSTO staff members wrote to Sutherland Shire Council on March 3, 2000, saying, inter alia: “We understand that ANSTO has been obtaining supplies of samarium from South Africa since the HIFAR shutdown in February with no dislocation, this isotope is usually manufactured by ANSTO. It is further understood that ANSTO has stopped its importation of samarium from South Africa to “prove” the need for a new reactor. If this is the case it would appear that ANSTO is orchestrating its own circumstances to ensure a new reactor.”

It is understood that ANSTO is supplying samarium at a price lower than the Medicare rebate, thus providing doctors with a
financial incentive to choose samarium over the equally- or more-effective imported radiopharmaceutical stronium-89 chloride (Metastron). This issue is of significance because Quadramet is one of the few therapeutic/palliative products produced by ANSTO, and also because of the short half life (47 hours) of Sa-153. ANSTO said in a submission to the Senate inquiry into the contract for a new reactor (2000) that it has exported samarium-153 to New Zealand which adds weight to the argument that importation is possible.

Nycomed Amersham said in its 1993 Research Reactor Review submission that “possible supply solutions could be found using Pacific Basin or European reactors as appropriate” for rhenium-186 and samarium-153.

Samarium-153 is just one of a number of radioisotopes with applications in bone cancer therapy or palliation - these include strontium-89, phosphorus-32, and rhenium-186. See Ben-Josef and Porter, 1997. See also discussion paper at <www.geocities.com/jimgreen3/samarium.html>

Price comparisons between ANSTO and alternative suppliers to the Australian market cannot be made. ANSTO’s major competitor in the radioisotope market, Nycomed Amersham, has supplied its price list but ANSTO refuses to do so.

Nothing is to be gained by listing the plethora of unsubstantiated claims made in the past 5-10 years regarding costs, but two points should be made:
* ANSTO’s Chief Executive (letter to Mayor of Sutherland Shire Council, April 7, 2000) says that “some essential radioisotopes” for medicine and industry have been imported during the February-May 2000 shutdown of HIFAR “at a significantly increased cost”
* two ANSTO scientists (personal communications, 1999-2000) have stated that Mo-99 supplied to ARI by the Nuclear Energy Corporation of South Africa is cheaper than that usually supplied to ARI by ANSTO

Should raw data on radiopharmaceutical costs become available, a comparison would need to address factors such as the level of subsidisation of ARI by ANSTO. According to an ANSTO scientist (personal communication, 1997), comparing costs between domestic and imported products “depends on how you make up the rules for determining them”. The costing of radioisotope production, as one component of multipurpose research reactor programs, necessitates some contestable assumptions such as the proportion of reactor operating costs and waste management costs to attribute to radioisotope production.

As at 1992-93, ANSTO charged ARI the marginal costs of radioisotope production - the costs of extra fuel, labour, and materials required to produce radioisotopes. The fee charged to ARI did not consider reactor costs (capital costs, operating costs, decommissioning costs), site costs, or “back-end” costs associated with radioactive waste management and reactor decommissioning. Since the September 1997 decision to replace HIFAR, ANSTO has claimed that there is no longer any subsidy of any sort to ARI.

ANSTO has not provided further details to support this claim despite being requested to do so.
Question: (Jim Green, letter to ANSTO, June 24, 1998): “ANSTO claims that products under the ARI trademark incorporate a charge made by ANSTO for the provision of waste management costs, reactor operating costs and all other site overhead costs. Could you please provide me with full details? Since when have the above provisions applied? What impact has this had on cost?”
Answer: (ANSTO’s Communications Manager, John Mulcair, December 22, 1998): “Details of the breakdown of ANSTO’s radioisotope production costs are commercial information as would be the case for all other manufacturers. Cross-charging for services associated with radioisotope production has been in place at ANSTO for more than 20 years.”

On the failure to account for capital reactor costs in the pricing of radioisotopes, the 1993 Research Reactor Review said: “Inasmuch as the capital invested in the HIFAR reactor is a sunk cost this is not unreasonable, but would not be appropriate for a new reactor.” However, ANSTO/ARI does not plan to increase radioisotope charges to hospitals/clinics to account for costs associated with the new reactor project. ANSTO’s Chief Executive Prof. Helen Garnett is quoted in the Australian Financial Review (24 September 1997) saying that no radioisotope producer is charged for capital reactor costs. However the Canadian company MDS/Nordion is investing over $C 100 million in two new reactors, with government funding for the balance of the $C 140 million project. Also, Nycomed Amersham has not been subsidised since it was privatised in the 1980s.

More recently, ANSTO responded to the above 1993 RRR comment with the evasive answer that: "ANSTO will continue to set its prices on a justifiable basis." (Submission to Senate inquiry, 2000.)

ANSTO’s 1998-99 Annual Report (p.91) provides the following figures for ARI:
* revenue $14.313 million
* total expenses $13.504 million (including $5.203 million “internal support”)
* operating surplus $960,000

As discussed above, there may be ongoing subsidisation of ARI by ANSTO which is not reflected in ARI’s figures on expenses and operating surplus.

Comparing the costs of imported versus ANSTO/ARI radioisotopes is also difficult because of the different product ranges of the various suppliers (comparing apples with oranges).

ANSTO’s Draft EIS (1998, p.4-7) says an Access Economics study estimates an annual net economic benefit of $8-10 million from medical radioisotopes. However the Access Economics study (p.4) claims gross economic benefits of $8-10 million annually. (The Access Economics study can be found at section 16 in the joint ANSTO / DIST submission to the Senate Economics References Committee (Nuclear Reactor Inquiry), 1998).

The report on ANSTO’s Draft EIS by Applied Economics Pty Ltd, appended to Sutherland Shire Council’s submission om the EIS, notes (p.10), “On page 4-21 (of ANSTO’s Draft EIS) it claims that reliance on imported radiopharmaceuticals would add to health costs and reduce the quality and reliability of health services. However, it does not quantify these claims. This is an important omission. Increases in health costs of say $1 million would be relatively insignificant compared with the capital and operating costs of the replacement reactor. Access Economics (1997) estimates that, if ANSTO were to stop producing radioisotopes, it would lose $8-10 million in gross revenue and that these losses would double in a few years. But, as the report points out, to obtain the net benefit to ANSTO it is necessary to deduct production and distribution costs. Moreover, the net benefit to reactor-produced radioisotopes should not include the value added from processing. If there were no reactor, the most likely scenario is that ARI would import Mo-99 and continue to produce most of the moly-generators supplied to Australian hospitals.”

Comments by Dr. Harvey Turner (see above) to the 1993 Research Reactor Review that doctors may have breached the Trade Practices Act, and at the same time used inferior quality products on their patients, are also relevant here. (Research Reactor Review, Transcript of Proceedings, Public Hearing, Perth, 23 March 1999, p.780.)

Increases in bulk radioisotope prices have a relatively small effect on hospital radiopharmaceutical budgets and an even smaller impact on overall costs associated with nuclear medicine (see Jim Green, 1998, submissions to Senate Economics References Committee (New Reactor Inquiry) and 1998 submission on ANSTO’s Draft EIS.)