Most of the medical submissions to the Senate inquiry were based on a brief form letter with no references to the medical/scientific literature and no attempt to justify the numerous assertions made. Even though most of the medical submissions went no further than rewriting the form letter, they contained numerous factual errors and numerous misleading claims, as discussed in following sections.

The inaccuracies in the medical submissions reflect the ignorance of many/most nuclear medicine professionals with respect to isotope production and supply options. This should come as no surprise: many nuclear medicine professionals have little or no experience in isotope procurement and still less experience in isotope production. The fact that Dr. Barry Elison, President of the Australian and New Zealand Association of Physicians in Nuclear Medicine (ANZAPNM), did not know about the February-May 2000 shut-down of the HIFAR reactor until July is proof positive that the permanent closure of HIFAR without replacement would have precious little impact on the practice of nuclear medicine.

The inaccuracies in the medical submissions also reflect financial self-interest. This topic was addressed by Dr. Barry Chatterton during public hearings of the 1993 Research Reactor Review (Adelaide, 24/3/93, pp.811-812 of transcripts): "One of the fears of the nuclear medicine doctors is that if radioisotopes were to become more expensive, Medicare schedule fees would not automatically reflect this, certainly not immediately. So increased costs would be absorbed by patients and/or practitioners."

The following strategy can be proposed should HIFAR be permanently shut-down without replacement:
- greater reliance on imported isotopes;
- 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 2-3 other capital cities are at various stages of advancement).
- 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; and
- 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:

1. All of the above strategies are based on EXISTING, FULLY-DEVELOPED, COMMERCIALISED technologies. For example there are three cyclotrons producing medical isotopes in Australia and about 250 cyclotrons producing medical isotopes around the world; already about 20% of the isotopes used in nuclear medicine in Australia are imported; and of course 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.

Dr. Barry Elison, President of the ANZAPNM, chose to ignore this point during the 26 October public hearing: "Alternate technologies - wonderful science - are not used commercially and will not be used commercially in the near future. ... We need something now not something in 25 years time."

2. None of these 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. This has been abundantly evident during the recent inquiry, e.g. Dr. Barry Elison (ANZAPNM - public hearing), e.g. Clarence Hardy (ANA - written submission), e.g. many of the medical form letters.

3. 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 isotope production technologies (primarily particle accelerators inc. cyclotrons) and alternative medical technologies will enable reduced reliance on imported isotopes.

4. 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.

Clearly the opportunity costs have been ignored by most or all proponents of a new reactor. For example Dr. Barry Elison (ANZAPNM, 26/10/00 public hearing) said that "The cost of approximately $300 million is a fair amount of money, but to actually say that that would buy better health care is a nonsense."

One of the few submissions to address the opportunity costs was Dr. Bill Williams, a Family Physician with 20 years experience (written submission, 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."

With respect to supply of molybdenum-99, which decays to form technetium-99m, used in about 75% of all nuclear medicine procedures, importation is the obvious, immediate option to HIFAR production.

There are several existing overseas suppliers of Mo-99 to Australia:
- Nycomed Amersham (weekly imports of Mo/Tc generators from Europe)
- Nuclear Energy Corporation of South Africa (regular / semi-regular shipments of bulk Mo-99 to ANSTO)
- Nordion/Canada (supply of bulk Mo-99 to ANSTO during HIFAR shutdowns).

Another supplier may emerge: Mr. Glen Pearce from Mallinckrodt Inc. (hearing, 4/12/00) said, "We are currently interested in reregistering our technetium generator to supply a section of the nuclear community. There are quite a few who are not happy with the current level of service or the actual generators that are being supplied - there are some problems with the current one. We are confident that we can be competitive in that current market, and we are looking at those situations at the moment."

Dr. Elison (ANZAPNM, written submission, volume 2) questions the reliability of imported Mo-99 but provides no evidence to substantiate the claim.

I have a letter from a past president of ANZAPNM in which he says he experiences only occasional delays with Mo-99 generator deliveries from Amersham/Europe and occasional delays from ANSTO, and he says cost is comparable. In addition, ANSTO scientists have repeatedly confirmed that ANSTO itself imports Mo-99 from the Nuclear Energy Corporation of South Africa on a regular or semi-regular basis, that the South African Mo-99 is cheaper than that produced by ANSTO, and that delivery from South Africa has been extremely reliable. A greater volume of Mo-99 has to be imported from South Africa to account for radioactive decay in transit, additional transport costs are incurred, and yet the South African Mo-99 is still cheaper than the heavily-subsidised Mo-99 produced by ANSTO and sold to ANSTO's radioisotope subsidiary Australian Radioisotopes (ARI).

It is noteworthy that Mallinckrodt, which supplies a substantial share of the USA market for Mo-99, chooses to supply the USA market from its production facility in the Netherlands. If supply was unreliable, Mallinckrodt would simply source Mo-99 from MDS Nordion (Canada) - or alternatively it would not have a substantial share of the USA market.

So greater importation of bulk Mo-99, followed by Mo/Tc generator manufacture by ARI, is the immediate, tried-and-tested option should HIFAR be closed without replacement.

Dr. Barry Elison (ANZAPNM, written submission, volume 2) says the cost of importing Mo-99 would lead to an increase in the cost of nuclear medicine services. However according to ANSTO scientists, Mo-99 from South Africa is cheaper than that supplied by ANSTO to ARI at a heavily subsidised cost.

Dr. Hugh Dixson (volume 2 of written submissions) says, "The importation of Mo-99 generators is, of course, possible. Apart from the expense of airfreighting heavy, lead lined generators to and from Europe, the lack of a local producer would remove competition from the market and lead to significant price increases." This ignores competition from overseas suppliers, of which there are several.

Dr. Elison (ANZAPNM, written submission, volume 2) says there are limited overseas sources. In fact there are several sources, e.g. MDS Nordion (Canada), Nuclear Energy Corporation of South Africa, Mallinckrodt (Netherlands), IRE (Belgium - processes targets irradiated in several European reactors) as well as other smaller producers of fission-product Mo-99. (A larger number of countries produce low specific activity "instant" Tc-99m using Mo-98 targets, but that is of no consequence.)

As the International Atomic Energy Agency said in IAEA Technical Document 1065, "Production Technologies for molybdenum-99 and technetium-99m", April 1999: "The present installed processing capacity [for molybdenum-99] is substantially larger than the demand (of about 6000 Ci per week (6-day precalibrated)), and the capacity for irradiation of targets is even higher. The large demand for Mo-99 has given it an 'industrial scale production' status."

Dr. Elison (ANZAPNM, written submission, volume 2) said, "ANSTO or ARI have done such a good job in establishing a distribution network and efficiently, so why break it? It works so well." Precisely! The immediate Mo-99/Tc-99m solution in the absence of a domestic reactor is importation of bulk Mo-99 to ANSTO followed by routine generator manufacture and distribution.

Dr. Elison (ANZAPNM, written submission, volume 2) says "All these latter difficulties have been recently exemplified during a scheduled shut-down of HIFAR reactor during which numerous delays were experienced with the supply of Mo-99m(sic)/Tc-99m generators. While ANSTO were (sic) able to minimise these impacts at considerable cost through some short term coping strategies, it should be pointed out that these were in fact short term, could not possibly have been utilised in the long term and would have resulted in a very inefficient, unreliable, and poor supply of radiopharmaceuticals for patient needs on a National basis." These are extraordinary comments given that Dr. Elison did not know the reactor was shut down until told about it in July. Indeed when told the reactor was shut down from February to May 2000, Dr. Elison's response was to deny that a shut-down had taken place, claiming he surely would have known about it!

Mr. William Hladik from Radiopharmacy Central (written submission, volume 6) says, "The only manufacturer of the Mo-99/Tc-99m generators that can supply them all across Australia throughout the workweek is Australian Radioisotopes (ARI), a division of ANSTO." This ignores the tried-and-tested option of importation of bulk Mo-99 followed by generator manufacture by ANSTO/ARI (and/or perhaps generator manufacture by other organisations - Radiopharmacy Central itself might play a role).

Mr. Hladik also said, "Foreign sources of Mo-99 cannot be depended on to supply this country due to the relatively small market here compared to North America and Europe (who are often given priority in supply), and especially during times of worldwide shortage of Mo-99, which occurs from time to time. On at least two occasions in the recent past, patient care has been compromised because foreign suppliers could not provide enough Mo-99 to Australia in a timely manner." Both these assertions are highly questionable and Mr. Hladik should be asked to substantiate them.

Dr. Barry Chatterton (written submission, volume 1) says, "When the Australian Nuclear Reactor is "down" it has proved possible to import very high activities of Mo-99 from overseas to maintain the production of technetium generators. This has enabled the majority of Australian practices to use the essential radionuclide for modern nuclear medicine, Tc-99m for which there is no real alternative. Shipping from the Northern hemisphere requires a long delay, and transport of activity sufficient to meet Australia's need on a weekly basis makes the 100+ departments in the country very vulnerable to a single reactor or transport failure. There is an internationally agreed transport index for radioactive materials which would make it difficult to increase quantities."

In response to Dr. Chatterton's comments:
- he appears to believe Australia would be dependent on a single overseas reactor for Mo-99, i.e. he doesn't know the first thing about the international isotope situation despite being one of the loudest supporters of a new reactor.
- shipping from the Northern hemisphere does not require a "long delay" as Dr. Chatterton asserts.

Mr. Glen Pearce from Mallinckrodt Inc. (hearing, 4/12/00) said, "The question as I see it is: can we import enough molybdenum? ... Can we import enough molybdenum to cover the Australian market? I believe the answer is yes, we can do that. The other question is: can we import generators to supply the Australian market? I believe that we can produce some, but we cannot sustain the entire market." As discussed, bulk Mo-99 importation is not only satisfactory, it would be the preferred immediate option in the absence of a reactor, e.g. ANSTO imports bulk Mo-99 during reactor shut-downs.

Questions about the cost of Mo-99 generally, about overseas suppliers raising prices in the absence of a domestic producer, and several other furphies were addressed by Mr. Todd Donaghy from Mallinckrodt Inc. (public hearing, 4/12/00):

"In the short term there is no advantage in producing it locally. You are in a better cost position to import the molybdenum. There is a worldwide market for molybdenum, and there is a basic market price that a number of companies compete on to maintain a price around a respectable level. There are at least six or seven companies that can supply molybdenum."

"Another issue that the previous witnesses have stated is reliability and the concern that the importation of molybdenum into Australia is potentially unreliable because of the world market. They believe that Australia is just a small fish in relation to that size but again I refute that. Mallinckrodt has a significant history of exporting molybdenum and a number of other radioisotopes out of its facilities in Petten and in Maryland Heights in the United States. Currently, it is estimated that they would ship between 7,000 and 10,000 packages per week to worldwide markets, Australia being one of them. We have a long and consistent history of shipping product and getting it there on time regardless of where it is in the world."

"There were some concerns that during times of worldwide shortages the smaller markets would suffer. I would suggest that that is unlikely to be the case. What has happened in the last few years with the molybdenum market worldwide is that companies have got together to ensure each other’s supply to their markets around the world. They have a primary supplier. They also have a backup and maybe a second or third backup from there."

"Importing it [molybdenum] would not, in the short term, produce any added cost. In the long term, if you are producing your own molybdenum you can look at economies of scale and get your unit cost down. Essentially, you could pass that on to the consumer, but it is unlikely to happen."

"It [Mo-99] is regularly imported into countries around the world. For example, our largest market is the United States. We do not produce molybdenum in the United States. We have a weekly shipment, from Petten in the Netherlands to Maryland Heights, of molybdenum and we produce all of our generators from that source. It happens on a weekly basis."

For the purposes of the current Senate inquiry, there is no need to investigate non-rector methods of Mo-99/Tc-99m production given the abundance of evidence demonstrating the viability of importation. Nevertheless a brief summary is included since the issue has been raised in several submissions.

Lyndell Oates (written submission #71, volume 2) said: "[T]here is no known viable method available for the production of our most commonly used radioisotope technetium-99m except as a by-product of nuclear fission i.e. reactor production." This ignores:
- non-reactor-based neutron generation, e.g. spallation technology
- non-neutron generation of Mo-99 and/or Tc-99m, e.g. the various accelerator methods.

Dr. Chatterton (written submission, volume 1) says, "If the opposition to the nuclear reactor believes accelerator produced technetium is economically possible, will they propose an intensive research and development process, funded in Australia, so that we may market this around the world? Would any be prepared to invest their own funds to reap the benefit if successful? If the answer is yes, my patients will still need a secure supply of radionuclides until the research has been completed and disseminated."

Dr. Chatterton's rant is perhaps best ignored, but for the record: yes, an intensive government-funded R&D process to commercialise a non-reactor method of Mo-99/Tc-99m would be desirable in Australia. In the interim, importation of bulk Mo-99 is the proven option.

Dr. Barry Elison (ANZAPNM President, written submission, volume 6) challenges opponents of a reactor to explain why commercial production of Tc-99m hasn't been implemented elsewhere if it is so attractive. In brief, non-reactor methods of Mo-99/Tc-99m are not in full-scale production because - with the exception of a largely wasted window of opportunity through the mid-1990s - there has been little or no incentive to develop a non-reactor method because of the easy availability of reactor-produced Mo-99/Tc-99m.

While importation of bulk Mo-99 into Australia is a tried-and-tested option to domestic Mo-99 production, the issue of accelerator production of Mo-99/Tc-99m (globally and/or Australia) is important for the following reasons:

First, Tc-99m is likely to remain the "workhorse" of nuclear medicine for the foreseeable future (notwithstanding the capacity of some cyclotron-produced radioisotopes, such as FDG, to replace Tc-99m and other reactor-produced radioisotopes for some clinical applications). Tc-99m is used in about 75% of all nuclear medicine procedures. With the successful development and widespread implementation of an accelerator technique for Mo-99/Tc-99m production, over 90% of the radioisotopes used in nuclear medicine would be produced using accelerators.

Second, large-scale reactor production of Mo-99 is of particular concern in relation to the generation of radioactive wastes, because the process involves the use of enriched uranium targets and the waste stream includes uranium fission products. A case in point is the trouble ANSTO has had with liquid intermediate-level wastes arising from Mo-99 production.

Third, the risk of radioisotope production facilitating covert production of nuclear weapons is most acute for Mo-99 production, because of the use of highly-enriched uranium targets by a number of commercial Mo-99 producers. According to Bennett et al. (1999), production of the annual supply of Mo-99 for the US market involves the use of over 40 kg of highly-enriched uranium (HEU). This amount is sufficient for several nuclear weapons. Reflecting international concern over the use of, and trade in, HEU, the Reduced Enrichment for Research and Test Reactors program has been working for some years to replace HEU reactor fuels with low-enriched uranium (LEU) fuels around the world and to replace HEU targets with LEU targets or non-uranium targets (Rojas-Burke, 1993; Vandegrift et al., 1999). While these issues are of concern internationally, it should be noted that ANSTO plans to use LEU fuel and LEU targets if a new reactor is built in Australia.

Fourth, reactor production of Mo-99 requires complex and expensive facilities for extensive handling, separation, storage and disposal of fission-type radioactive products, by-products and waste. Global supply is dominated by a small number of producers because of this complexity and expense (among other reasons).

As Bennett et al. (1999) note, "An alternative source of Tc-99m will be well received if it is competitive in cost with the currently subsidized supply and if it avoids the environmental hazards and political liabilities of the current nuclear-reactor-based technology."

There are numerous methods of using accelerators to produce Mo-99 and/or Tc-99m. Some show little or no promise, but several have been the focus of research and development efforts and have generated debates revolving around a number of interconnected technical, logistical, and economic factors - production yields, target cooling, target purity, specific activity and purity of cyclotron-produced Mo-99/Tc-99m, and last but not least, cost.

Research into accelerator production of Mo-99/Tc-99m has lost momentum in the past five or so years. The main reason is the construction of two new research reactors in Canada which will be dedicated to radioisotope production and Mo-99 in particular. Each of the Maple reactors will have the capacity to produce more than 100% of the world's demand for Mo-99, xenon-133, iodine-131 and iodine-125, and they will have the capacity for increased production to meet any foreseeable growth (Anon., 1999).

According to the International Atomic Energy Agency (IAEA, 1999), "The presently installed processing capacity is substantially larger than the (global Mo-99/Tc-99m) demand, and the capacity for irradiation of targets is even higher. Due to the existing investment in production infrastructure and in the approval of Mo-99 and derived products, there will have to be a substantial economic incentive for a large producer of Mo-99 or Tc-99m generators to change to a new process."

Several producers - using reactors and processing facilities in Canada, South Africa and Western Europe - supply almost the entire global demand for Mo-99/Tc-99m. With the construction of two new dedicated reactors in Canada, the production capacity will be further increased.

Little research is currently underway specifically investigating accelerator production of Mo-99/Tc-99m. However research in related fields is directly relevant to accelerator production of Mo-99/Tc-99m and could spark renewed interest. Examples include:
- the development of cyclotrons with higher beam intensities, for the production of therapeutic radioisotopes such as palladium-103 (Jongen, 1999);
- ongoing research into the Myrrha spallation system (discussed below), currently focused on scientific applications but using the same spallation source design as originally envisaged for Mo-99 production (SCK-CEN, 1998, pers. comm.); and
- the development of new generator types suitable for low specific activity Mo-99/Tc-99m (whether produced in reactors or accelerators).

Ongoing problems with radioactive waste management could also generate renewed interest in accelerator methods of Mo-99/Tc-99m production. According to a 1993 article in the IAEA Bulletin, many operators of research reactors find themselves in a "crisis situation" because of waste management problems (Takats et al., 1993). Where a "solution" has been found, it has often been the shipment of spent fuel to the USA (which has supplied enriched uranium fuel for many research reactors) or to other countries - really a shifting of the problem rather than a satisfactory solution. According to the International Atomic Energy Agency (1999), "When modifications to existing processes or the possible implementation of new technologies (for Mo-99/Tc-99m production) are considered, the implications regarding waste management and treatment and disposal should receive high priority."

Several overseas research projects have investigated methods to produce Mo-99 and/or Tc-99m using accelerators over the past decade. Arguably the following three are of greatest interest.

Electron accelerator, Mo-100 target, separation of Tc-99m

This project involved a multidisciplinary team of researchers from the Idaho National Engineering and Environmental Laboratory (INEEL) and Lockheed Martin Idaho Technologies Company (Bennett et al., 1999). The process involved an electron accelerator producing electrons used to bombard a tungsten plate, thus producing gamma rays used to bombard enriched Mo-100 targets, thus producing Mo-99 from which the decay product Tc-99m could be extracted through a sublimation process. (Separation and use of Mo-99 is not technically feasible.) Bennett et al. (1999) estimate that one such facility would cost US$3.7 million with annual operating costs of US$1 million; thus the entire US demand could be met with 20 facilities and the Tc-99m sold for an unsubsidised cost lower than the current subsidised price.

Substantial research and developmental work has taken place with this project but it is currently stalled because of lack of interest from the US Department of Energy and private-sector interests. According to Dr. Ralph Bennett from INEEL, private-sector companies decided not to pursue the project in light of the improving picture for reactor-based supplies of Mo-99 (pers. comm, January 2000). According to Bennett, "I believe that there is a considerable fear on the part of potential commercial partners that the subsidized foreign supplies would act to cut their prices to preserve jobs and national pride. There was also uncertainty about the cost of the effort required to get FDA approval."

Cyclotron, Mo-100 target, separation of Tc-99m

This research is most closely associated with Dr. Manuel Lagunas-Solar (1999) and others at the University of California (Davis). An IAEA (1999) technical document summarised the technique in these words:

"The production of Tc-99m via the Mo-100(p,2n) reaction was evaluated, and the cross section data available were found to be consistent and in good agreement. Extrapolating Tc-99m yields obtained from this data, using the operational conditions of existing 30 MeV accelerator technologies ... suggest that large scale (kCi) production of Tc-99m is possible."

"With this approach, with available accelerator and target technologies, logistical factors would prevail for local/regional production and distribution. However, the 'instant Tc-99m' approach is being utilized successfully, particularly in developing countries operating research reactors. A distinct advantage of this new approach is the possibility to produce and provide single photon radiopharmaceuticals (i.e. thallium-201, gallium-67, iodine-123 and indium-111), therapy radionuclides (i.e. Pd-103, iodine-124, etc.) as well as positron emitting radionuclides such as fluorine-18, carbon-11, oxygen-15, nitrogen-13."

As the IAEA (1999) technical document goes on to note, further research and developmental work is necessary to determine the feasibility of using this technique for large-scale production of Tc-99m.

Hybrid cyclotron/spallation system, uranium target, Mo-99 production

A research and development project, known as Myrrha, based at the Belgium Nuclear Research Centre (SCK-CEN) aims to replace the aging BR-2 research reactor with an accelerator-driven spallation system. (Spallation reactions result from the interaction of very high energy particles with nuclei in the target material, yielding a large number of disintegration products.)

The objectives of the Myrrha project as at late 1997 were to design and construct a small-scale prototype advanced accelerator-driven system. Potential applications include scientific research, industrial applications, radioactive waste transmutation, power generation and radioisotope production. As at January 2000, SCK-CEN was, in collaboration with nine national and international partners, conducting a "pre-design" of the Myrrha system (SCK-CEN, pers. comm.).

The proposed Myrrha system will be driven by a cyclotron, not by the sustained uranium fission reaction of a research reactor; in fact design features exclude the possibility of uranium fission criticality. Thus the system will be advantageous when compared with research reactors on safety grounds, and it will not generate fission fuel wastes.

In the mid-1990s the project was focused on the potential to use such a system for Mo-99 production; this was the "Adonis" project (Accelerator Driven Operated Nuclear Irradiation System), a collaboration between SCK-CEN and Ion Beam Applications (IBA - a company which manufactures cyclotrons). Most of the research into accelerator methods of Mo-99/Tc-99m production has focused on direct Tc-99m production. A significant advantage of an Adonis system, when compared with accelerator or reactor production of "instant" Tc-99m, would be production of the longer-lived parent, Mo-99, thus enabling long-distance transportation.

While the Adonis project evolved into the broader Myrrha project several years ago, progress remains of considerable relevance for Mo-99 production. Whether a systematic effort is made to develop a system for Mo-99 production will depend on a range of factors, of which the status of reactor production is a key one. The Department of Industry, Science and Tourism and ANSTO (1998), in a joint submission to the Senate Economics References Committee, said, "An expert from IBA discussed the ADONIS concept at the IAEA Consultants Meeting on Molybdenum-99/Technetium-99m Technologies in Capetown in April 1997. He said that he appreciated that the likelihood of Adonis getting off the drawing board was adversely affected by the then recent decisions to proceed with the Maple (Canada) and the Sandia (USA) proposals for reactor production of molybdenum-99."

More information on Myrrha/Adonis: Jongen (1995; 1999); SCK-CEN, n.d.; Zeyher, 1997.

References

Anon., 1999, "MDS Nordion's MAPLE Reactors on Schedule", Journal of Nuclear Medicine, Vol. 40(6).

ANSTO, 1998, Replacement Nuclear Research Reactor: Draft Environmental Impact Statement, Volume 1.

Bennett, Ralph G., et al., 1999, "A System of Tc-99m Production Based on Distributed Electron Accelerators and Thermal Separation", Nuclear Technology, Vol.126, April, pp.102-121.

International Atomic Energy Agency, 1999, Summary: Technical Document 1065, Production technologies for Molybdenum-99 and Technetium-99m, IAEA: Vienna, pp.1-3.

Jongen, Yves, et al., 1995, "A Proton-Driven, Intense, Subcritical Fission Neutron Source for Radioisotope Production", Proceedings of the International Conference on Accelerator-Driven Transmutation Technologies, Vol.346(1), pp.852-857.

Jongen, Y., 1999, "High Beam Intensities for Cyclotron-Based Radioisotope Production", in International Atomic Energy Agency, Technical Document 1065, Production technologies for Molybdenum-99 and Technetium-99m, IAEA: Vienna, pp.133-138.

Lagunas-Solar, M.C., 1999, "Accelerator production of Tc-99m with proton beams and enriched Mo-100 targets", in International Atomic Energy Agency, Technical Document 1065, Production technologies for Molybdenum-99 and Technetium-99m, IAEA: Vienna, pp.87-112.

Rojas-Burke, J., 1993, "Ban on Enriched Uranium Exports Intended Against Bomb Builders also Affects Radiopharmaceutical Makers", Journal of Nuclear Medicine, Vol.34(3), pp.19N-40N.

SCK-CEN, n.d., "The Adonis Project", <www.sckcen.be/scientrep/96/scrrsrp/lvd1.html>

Takats, F., Grigoriev, A., and Ritchie, I.G., 1993, "Management of spent fuel from power and research reactors: International status and trends", IAEA Bulletin, No.3, pp.18-22.

Vandegrift, G.F., et al., 1999, "Converting targets and processes for fission-production molybdenum-99 from high- to low-enriched uranium", in International Atomic Energy Agency, Technical Document 1065, Production technologies for Molybdenum-99 and Technetium-99m, IAEA: Vienna, pp.25-74.

Zeyher, Allen, 1997, "Belgian Companies Propose New Solution for Isotope Production", Journal of Nuclear Medicine, Vol.38(3), p.16N.

Lyndell Oates (written submission #71, volume 2): "Although supply from overseas is at the current time possible it is not unreasonable to expect that other countries may also be reviewing the production of radio-isotopes as we are here." Indeed they are: in the mid to late-1990s, there were plans for a 10 MW reactor in Indonesia dedicated to isotope production, but this was dropped because of the global over-capacity of isotope production; the US plan to use the Sandia reactor for Mo-99 production is dead because of the global over-capacity of isotope production and because supply can be so easily obtained from elsewhere; in Belgium the plan is to replace the BR-2 reactor with a spallation source; and so on. In the global context it is nonsensical to argue that Australia (or the world) needs another source of reactor-produced isotopes.

It is interesting to note that although the Australian Nuclear Association (written submission, volume 2) supports a new reactor on medical and other grounds, the ANA "accepts that it would be possible to import a large proportion of the required [medical] isotopes" and Dr. Hardy said during a public hearing, "you would have read all the submissions and many doctors and practitioners in nuclear medicine are strongly supportive of this proposal. They admit that you can import radioisotopes, and I admit that too: you can import radioisotopes". Similar comments were made by Dr. Barry Elison (ANZAPNM) and others.

Dr. Peter Robins (written submission, volume 2) says "In Western Australia we are and always have been acutely aware of the problems of distance and transportation of short and medium half-life radioisotopes for both diagnostic and therapeutic use. Patient care is directly affected by limited deliveries of some isotopes from overseas and it is only through a ready supply within Australia that we are able to offer a timely and cost efficient service in an isolated geographical location such as Perth." This is at odds with the comments of a nuclear medicine physician in WA (and past president of the ANZAPNM) who has written to me saying that Mo-99/Tc-99m generator delays from both ANSTO and an overseas supplier occur "occasionally".

Dr. Barry Elison (ANZAPNM, written submission, volume 6) makes the following assertions, without providing any evidence or any references to the literature:
- as "dangerous goods", isotopes are subject to complex IATA rules;
- pilots, foodstuffs and animals are all potential causes for isotopes to be off-loaded
- each type of aircraft can carry a limited Transport Index total
- isotope shipments require approved packaging
- all dangerous goods are subject to full fares, no discount freight rates apply
- "It is estimated that approximately 5% of even the relatively few imports at present experience significant deviations from their anticipated shipping schedules."

If international transport of radioisotopes is so onerous, why is it that:
- over three-quarters of all nuclear medicine procedures carried out all over the world use imported isotopes?
- over two-thirds of all nuclear medicine procedures carried out all over the world use Tc-99m milked from imported Mo-99?
- advanced industrial countries with numerous domestic research reactors, such as the USA, UK and Japan, rely on imports and cyclotrons for over 90% of their isotope requirements?

The Research Reactor Review (a.k.a. the McKinnon report, p.224) concluded that countries importing radioisotopes had either overcome logistical problems with importation, or found them not to be a problem in the first place.

Dr. Denis Gribbin (RANZCR, public hearing 26/10/00) said, "Australia’s geographic isolation and small population give it a low priority and leverage in the global marketplace compared to other countries." The Research Reactor Review (1993, p.94) noted that there was no evidence of overseas suppliers interrupting Australian supply in favour of larger, more lucrative markets. Moreover this argument assumes shortages of supply which are unlikely to occur given the investments of the major radiopharmaceutical companies in recent years. The Senate Committee might like to ask Dr. Gribbin if he can supply even a single example.

Dr. Gribbin (RANZCR, public hearing 26/10/00) also made a number of unsubstantiated assertions about the relative costs of ANSTO/ARI and imported isotopes. Those comments should be ignored unless Dr. Gribbin can provide substantiating evidence. Should the Senate Committee choose to pursue the issue of costs, ANSTO's subsidisation of ARI will need to be taken into account. Determining the extent of this subsidisation is difficult because ANSTO asserts that it involves commercial-in-confidence issues. More information on cost issues is available on request.

Dr. Christopher Rowe (written submission, volume 6) said imported radioisotopes, e.g. indium-111, are noted for their high cost. This is a nonsense statement. Indium-111 is cyclotron-produced and thus it's availability, cost etc. has nothing whatsoever to do with the reactor debate. If overseas suppliers were substantially more expensive than ANSTO's (subsidised) products, no doubt numerous pro-reactor submissions would have provided concrete cost data to prove the point. No such data has been provided. Indeed ANSTO will not even supply it's price list to allow for comparisons (whereas Nycomed Amersham has provided me with its price list).

When asked if any medical radiopharmaceutical used in nuclear medicine could not be imported into Australia, Mr. Donaghy from Mallinckrodt Inc. said:
 

"I would suggest, no. The only reason it would not be imported at the moment is because it is not registered with the TGA. However, you could have access to it. You could get approval under schemes such as the Special Access Scheme which currently some isotopes or pharmaceuticals are imported under to use in special cases with patients. I would suggest there would be no product, given the correct approvals, that could not be brought in."

"Yes, but there are going to be situations or different characteristics where there may be a concern. For example, isotopes that have short half-lives may have to leave their overseas production facility in large quantities if the physician here is to get the required amount into this country, and there would be a cost factor with that. But, essentially, there is no product that cannot be physically imported into the country."

Dr. Barry Elison (ANZAPNM President, public hearing 26/10/00) said, "We are faced with a situation in Australia. We are separated by tyranny of distance in many instances, but in the field of medical isotopes we really do suffer from that." Neither Dr. Elison nor any other supporter of a new reactor provided any evidence to substantiate such assertions.

Mr. Pearce from Mallinckrodt Inc. (hearing, 4/12/00) said, "For us, as importers, once we get our sources cleared through customs, that is when the fun begins and that is where we experience most of our difficulties. Mallinckrodt has over 30 years experience in importing pharmaceuticals into the Australian market. While we have had a few delays, we are very confident in our supply channels and in our ability to supply the Australian market. Several of our customers can vouch for our high level of customer service and our reliability over that 30-year period. We have three regular deliveries per week. We bring in thallium, gallium, indium and yttrium on those three deliveries, basically every week of the year."

A number of pro-reactor submissions, including those based on a form letter, cried crocodile tears about the "coping" mechanisms employed during the three-month reactor shutdown. One wonders how many of these doctors even knew the reactor was shut down until they were asked to make a submission to the Senate inquiry and supplied with a form letter to that end.

It was further argued that a permanent HIFAR closure would pose even greater problems than a temporary shut down. A more likely scenario is that if HIFAR was permanently shut down, some teething problems arising from greater reliance on imports would arise and they would be resolved. Comments from Mr. Donaghy from Mallinckrodt Inc. (public hearing, 4/12/00) are relevant here:

"There is, however, the situation where sometimes paperwork is not done correctly or airlines may off-load product as it moves about the world. Mallinckrodt have been shipping products around the world for many years now. They rely on their good relationships with airlines and their experience in making sure the paperwork is done correctly. I can speak from our company’s point of view to say that it would be a very small percentage of our product that would not arrive at its destination on time and intact due to the experience we have in shipping and with the paperwork. We have a wonderful relationship with the airlines in getting the product from point A to point B."

Mr. Donaghy also noted that long-term contracts would be advantageous:

"In this day and age of contracts and supplying, you would enter into a contract with a company. If it were Mallinckrodt, it would agree to supply you with X amount of molybdenum per week over a period of, say, 12 months. Part of that contract would be that if they were not the primary source due to whatever situation that may arise, a secondary source would more than likely be named in that contract. I would suggest that that would be the situation."

A number of pro-reactor submissions, including the medical form letters, made unsubstantiated claims about limitations on the amount of radioactivity that can be carried by air. This is a furphy and the fact that these claims were parroted in so many submissions is itself revealing.

Mr. Donaghy from Mallinckrodt Inc. (hearing, 4/12/00) said, "Another of the main concerns brought up relates to the transportation, the shipping via airlines into Australia. There is an index which controls the amount of radioactivity that can be placed on any airline, which is a TI or transport index. Most of the airlines set this index at a certain level so that only a certain amount of radioactive product can be placed on that airline. There is no problem in shipping any type or amount of molybdenum worldwide because of the shielding and packaging material that is used. If the product exceeds this TI the normal practice is to add more shielding to it thereby protecting anybody else or any other product that may be on that plane."

Mr. Donaghy also noted: "There is no problem in shipping any type or amount of molybdenum worldwide because of the shielding and packaging material that is used. If the product exceeds this TI the normal practice is to add more shielding to it thereby protecting anybody else or any other product that may be on that plane."

The USA radiopharmaceutical market is about 40 times bigger than the Australian market, and the Japanese market is about 27 times bigger (according to ANSTO, 1993, First Round Supplementary Public Submission to the Research Reactor Review). Yet plans to reinitiate Mo-99 production in the USA have been scrapped because of the availability of overseas sources. Japan gets its Mo-99 from MDS Nordion/Canada and has no plans for domestic production.

DISR/ANSTO (written submission #119, volume 3) say "Because the United States has had an extended reliance on imports of some isotopes from Canada for the last decade or so, a research reactor was brought to a stand-by condition in 1999 for the production of molybdenum-99."

This is a disingenuous way of saying that the project has been shelved - for the simple reason that ample Mo-99 supply can be obtained from Canada and Europe. This is confirmed in the April 2000 Final Report of the Nuclear Energy Research Advisory Committee (NERAC) Subcommittee for Isotope Research & Production Planning, which says "The recently refurbished Hot Cell Facility at Sandia National Laboratory has 12 cells which are connected together to accommodate processing of molybdenum-99. Sandia was given the mission to produce a backup supply of this commercial medical isotope in 1996, and began a major upgrade of its facilities. However, the program was halted in 1999 as other commercial supplies were brought online before its completion."

A 1999 paper said the Sandia initiative "stalled for lack of funding". (A. J. Kuperman, "A level-playing field for medical isotope production - how to phase out reliance on HEU", Paper Presented at 22nd International Meeting on Reduced Enrichment for Research and Test Reactors (RERTR), Budapest, Hungary, October 7, 1999. <http://www.nci.org/rertr99.htm>.)

There are several debates over alternative technologies:
- alternative clinical technologies, e.g. MRI, CT
- non-reactor methods of producing isotopes (including cyclotron production of Mo-99/Tc-99m, cyclotron production of therapeutics, cyclotron production of PET isotopes)
- alternatives to radioisotopes for research, in vitro studies etc.

As discussed above, the closure and non-replacement of HIFAR would have negligible impact on nuclear medicine even without any further technological advancement in these fields. Pursuing alternative technologies instead of a new reactor is not a "risky step" as was suggested by Senator McLucas on 26/10/00.

Drs. Bibbo and Cain (written submission, volume 1) say "At present, there are no alternative modalities to nuclear medicine and it is envisaged there will not be in the future." This is not true. The competitive relationship that exists between nuclear imaging and other diagnostic imaging modalities was addressed by Dr. Barry Chatterton (written submission, volume 1): "Over the years, the 'market' has caused the extinction of once thriving nuclear techniques such as the nuclear brain (blood brain barrier) and liver (colloid) scanning (superior methods for these indications such as brain CT and MRI were developed)."

Dr. Elison (ANZAPNM, public hearing, 26/10/00) discussed the competition between nuclear medicine and other technologies: "Nuclear medicine is an evolving technology. We are always faced with competing technologies. In the early part of nuclear medicine back in the 1960s we were imaging thyroid glands better than x-ray was doing it. x-ray evolved into new technologies such as ultrasound and they do a very good job in looking at the stuff. We have then developed technologies which show how things work. So of course we have to develop competing technologies. We have to be good. Sensitivities of detection of 90 per cent are not good enough; we are aiming for 100 per cent. That is what Dr. Jacobson is talking about. There are many other articles in our own local literature and elsewhere encouraging our young scientists to find better ways of competing. Of course you have to compete. If you did not have competition you would not have technology such as MRI or advanced ultrasound."

Oddly, Dr. Elison also said, "There are certain things that nuclear medicine is used for. It is unique, and at this stage there are no alternate technologies."

In the absence of a domestic reactor, 98-99+% of nuclear medicine procedures will be unaffected; alternative products and procedures will fill the void left by the non-availability of a few infrequently-used isotopes.

The growth of PET (discussed below) is also relevant to this discussion of alternative clinical technologies.

Dr. Michael Kitchener, a Past President of the ANZAPNM (written submissions, volume 1) says "The suggestion that it (PET) will replace standard nuclear medicine techniques is not borne out by the evidence."

Who has made such a suggestion? This is a ‘straw-man’ argument. There is a long history of various imaging/diagnostic technologies finding clinical niches, sometimes pushing other technologies out in the process, sometimes being overtaken themselves. Within the field of nuclear medicine there is a fluid process of radioisotopes finding niches, being replaced, and so on. The momentum within nuclear medicine has been towards ever-greater reliance on Tc-99m. If a sustained trend away from Tc-99m does occur, it is unlikely to happen quickly. It is conceivable but unlikely that any particular radioisotope (or system such as PET) will emerge to rapidly and fundamentally alter the practice of nuclear medicine, overtaking Tc-99m along the way. If a trend away from Tc-99m does develop, it is more likely to be gradual and uneven. As with research into new production methods, the likelihood of ample supplies of fission Mo-99, for the next generation at least, may act as a brake on efforts to replace Tc-99m with other radioisotopes such as FDG and iodine-123.

(FDG is F18-fluorodeoxyglucose, the main PET radiotracer.)

The enthusiasm about PET comes from the medical profession, not from those concerned with the Lucas Heights reactor proposal. For example, Dr. Henry Wagner describes FDG as "the Molecule of the Century". (The Journal of Nuclear Medicine, Vol.41 No.8, August 2000).

In the USA, the estimated number of FDG PET studies was 69,000 for 1998, 106,000 for 1999, and "at least" 155,000 studies for 2000 (Dr. R. Edward Coleman, "Clinical PET: Role in Diagnosis and Management", The Journal of Nuclear Medicine, Vol. 41 No. 8, August 2000.

PET (esp. FDG PET) has already replaced reactor-produced isotopes for some indications and the growing availability of PET isotopes (and appropriate imaging equipment, whether dedicated PET facilities or SPECT) may allow for further displacement. Complete replacement of standard nuclear imaging by PET has never been raised by any-one except as a straw-man by the doctors. This issue was dealt with in some detail in my submissions to the Senate Economics References Committee and in my PhD thesis (link from <www.geocities.com/jimgreen3>)

Dr. Gribbin (Royal Australian and New Zealand College of Radiologists, public hearing, 26/10/00) noted the growing role of PET in the USA: "In the United States, where they have had a greater market penetration of PET for much longer than we have, it is funded for specific diseases. It is refunded for lung nodules, for instance, where you are trying to work out whether it is a cancer or whether it is benign. Melanoma is funded, and some forms of lymphoma, and recurrent bowel cancer. It has been shown that with some forms of cancer it is not very useful so there is no funding for that."

Similarly, Mr. Barry Moore, President of the Royal Australian and New Zealand College of Radiologists (written submission, volume 1) says "It is acknowledged that there is a theoretical ability to reduce the reliance on reactor-produced medical isotopes for diagnostic imaging by greater use of cyclotron-produced isotopes, PET and FDG PET for appropriate indications. However, in practice the ability to reduce the demand for reactor-produced isotopes in this way is constrained by the current Commonwealth Government policy specifically barring the use of PET imaging as a substitute for conventional nuclear medicine, including F-18 bone scans. The significant cost of establishing the necessary infrastructure for widespread PET is also prohibitive."

More detailed information on PET can be found in my submission to the Senate Economics References Committee inquiry (volume 1).

Regarding chemical and biological alternatives to radioisotopes for research and in vitro studies, a useful summary paper by Party and Gershey can be found in Volume 4 of written submissions to the 1997-99 Senate Economics References Committee, pp.659-663. The reference is Party, E., and Gershey, E.L., 1995, "A Review of Some Available Radioactive and Non-Radioactive Substitutes for Use in Biomedical Research", Health Physics, Vol.69(1), pp.1-5.

Dr. M. McCarthy (written submission, volume 1) says all therapeutic radioisotopes are reactor produced. This is incorrect. Therapeutics such as palladium-103 and iodine-125 can be - and are - produced in cyclotrons.

DISR/ANSTO (written submission #119, volume 3) says "With the [proposed new reactor] it will be possible to produce in commercial quantities isotopes such as carrier-free holmium-166 and lutenium-177. HIFAR cannot produce these isotopes in HIFAR because of insufficient neutron flux. Other isotopes such as platinum-195m which can only be produced at a relatively low specific activity in HIFAR may be more attractive for therapeutic use with a new reactor of higher neutron flux."

The key words are "possible" and "may". We have been promised a new generation of therapeutic isotopes for some decades and it has yet to materialise. A study of therapeutic isotope usage in the UK in 1995 found that over 90% was iodine-131 in terms of administered radioactivity. (Clarke, S.E.M., Clarke, D.G., and Prescod, N., 1999, "Radionuclide therapy in the United Kingdom in 1995", Nuclear Medicine Communications, Vol.20, pp.711-717.)

In the USA, only four therapeutic isotopes have received FDA approval and are currently used. A Frost and Sullivan study found 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." (Frost and Sullivan, 1998, "Future of Nuclear Medicine, Part 3: Assessment of the U.S. Therapeutic Radiopharmaceuticals Market (2001-2020)", The Journal of Nuclear Medicine, Vol.39(7), p.14N-27N.)

It is notable that ANSTO/ARI "rationalised" its product line "to its financial advantage" some years ago (ANSTO, 1993, Submission to the Research Reactor Review, Attachment B: "The Need for a New Research Reactor in Australia", Working Paper 4: "Commercial Benefits of Reactor Operations".) In other words, low-volume, no-profit products were ditched. With a new reactor, it could be expected the financial pressures will be similar to, or greater than, they are now and low-volume, no-profit products will not be produced regardless of technical capabilities.

Dr. Patrick Butler (written submission, volume 1) says that over 6000 patients underwent nuclear imaging studies at St. George Hospital in 1999/2000, while there were over 200 nuclear medicine therapy patients (mostly iodine-131). Thus only 3.2% of all nuclear medicine procedures were therapeutic, which undermines the argument that a new reactor is a life-and-death matter with respect to isotope supply.

Dr. Elison from the ANZAPNM (written submission, volume 6) wrote: "In most therapy with radioisotopes, it is important that the radioactivity be used as quickly as possible after production while "fresh" in order to prevent the build-up of contaminants. This is obviously difficult with imported radioisotopes." However, according to an article in the IAEA Bulletin, a number of medical applications do not require radioisotopes with high specific activity, such as therapeutic bone agents (e.g. rhenium-186, samarium-153, holmium-166, yttrium-90), but other radioisotopes must have high specific activity such as those used in the emerging field of radioimmunotherapy using labelled monoclonal antibodies. (Vera-Ruiz, Hernan, 1985, "Radiopharmacy: New techniques spur growth", IAEA Bulletin, pp.48-49.)

According to Dr. Henry Wagner, "188-Re is likely to become very important in the future. It is available as the 17-h daughter of 188 W, which has -186 a half-life of 69 d. The cost of the 188-W generator is low enough to make possible extensive use of 188-Re as a therapeutic radionuclide, especially because of its chemical similarity to 99m-Tc. Over the next few decades. it is likely to become the therapeutic radionuclide of choice." (The Journal of Nuclear Medicine, Vol.41 No.8, August 2000).

The therapeutic isotope yttrium-90 was raised in some submissions.

Dr. Elison, (ANZAPNM President, 26/10/00 public hearing) said yttrium-90 has a 40-hour half life. In fact the half life is 64 hours - very similar to Mo-99 (66 hours) and Mo-99 is routinely transported all over the planet.

In addition to the option of importation of yttrium-90 itself, ANSTO’s Draft EIS (p.6-13) says that routine importation of carrier-free yttrium-90 is possible using a generator using "fission products extracted from spent fuel". In other words: yttrium-90 could be obtained from a generator containing the parent radioisotope, strontium-90.

Nycomed Amersham has imported yttrium-90 in the past and it may well still import yttrium-90. Other radiopharmaceutical companies operating in Australia may do the same. Indeed Mr. Pearce from Mallinckrodt Inc. (public hearing, 4/12/00) said that Mallinckrodt is importing yttrium-90.

Dr. Elison (ANZAPNM President, 26/10/00 hearing) said "mention was made of a strontium-yttrium generator. It is experimental. The problem is that the elution of yttrium from strontium is very slow. You do not get rapid production of yttrium." But is there any need for rapid production?

Colin Sutton from SIRTeX Limited (written submission, volume 1) says that over the past 5 years SIRTeX has treated about 500 patients with yttrium-90. This is a tiny fraction of all nuclear medicine procedures carried out in Australia: far less than one-tenth of one percent of the total.

Quadramet is a palliative for secondary bone cancers, based on the isotope samarium-153 which ANSTO produces. More info at <www.geocities.com/jimgreen3/samarium.html>

Dr. Hugh Dixson (written submission, volume 2) says that he was unable to obtain any Quadramet during the February-May HIFAR shut down. However anonymous ANSTO staff members wrote to Sutherland Shire Council on March 3, 2000, saying, "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."

ANSTO management said that the imported samarium was of poor quality and too expensive - but ANSTO refused a request to substantiate these claims. 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 Quadramet over the more commonly used alternative Metastron (strontium-89 chloride).

ANSTO's Helen Garnett said at the 9/10/00 public hearing that samarium-153 "cannot be imported." This flies in the face of the fact that ANSTO itself has imported samarium-153, and ANSTO's expectation (perhaps already realised) of establishing an export market for Quadramet.

Mr. Martin Carolan (written submission, volume 1) says there is a "large price differential" between Metastron (strontium-89 chloride, imported by Nycomed Amersham) and ANSTO/ARI's Quadramet. This mischievous statement ignores the fact that Metastron is effective as a palliative for far longer than Quadramet. According to a 1997 article in Annals of Medicine, Metastron is effective for an average of six months (range 4-15 months) compared with Quadramet - median duration of palliation = 2.6 months. (Edgar Ben-Josef and Arthur T. Porter, "Radioisotopes in the Treatment of Bone Metastases", Annals of Medicine, Vol.29, pp.31-35, 1997.)

Dr. Barry Chatterton (written submission, volume 1) asks the "opponents" of therapies such as Quadramet to put a dollar value on each day with an improved quality of life." This somewhat hysterical comment calls into question Dr. Chatterton's grasp on the substantive issues. There are numerous alternative to Quadramet for the purpose for which it is used - alleviation of pain associated with secondary tumours. Indeed Quadramet is not a front-line treatment. These issues were addressed in my first submission to the Senate Economics References Committee.

Samarium-153 has a half-life of 46-47 hours not 40 hours as stated by Dr. Elison (ANZAPNM, 26/10/00 public hearing).

With respect to strontium-89 chloride (Metastron), Dr. Turner (RANZCR, 26/10/00 hearing) said: "There is a similar agent, which is shipped from Amersham in Great Britain, and that is strontium-89. A patient may have to wait for one or two weeks in order to get that, and it has got been delivered on a specific day." In response:
- Metastron is delivered weekly by Nycomed Amersham;
- it has a half life of 50.5 days (according to ANSTO's Draft EIS) and so may not need to be used in the same week in which it is produced and delivered;
- in any event Metastron is patented and ANSTO could not produce it even if it wanted to; i.e. it is of absolutely no relevance to the debate over a new reactor.

Dr. N. Daunt (written submission #40) is concerned that without a new reactor the isotope strontium-87 for the secondary bone cancer therapy will not be available. In fact, it's strontium-89 not strontium-87 (more precisely, strontium-89 chloride, marketed as Metastron), and it has never been produced by ANSTO because it is patented by Nycomed Amersham and is imported into Australia.

The medical supporters of a new nuclear reactor rarely say anything about the radioactive waste problems arising from ANSTO's reactors, and when they do comment on the issue they are less than convincing.

Dr. Denis Gribbin (RANZCR, public hearing 26/10/00) said, "I would have to rely on others to speak on the disposal of the nuclear waste, and on the running of the reactor. I do not have any expertise in that, I have to rely on them. ... The way I look at it is that it has come out of the ground and we are just putting it back in the ground, burying it in shafts. That is perhaps an oversimplistic view of what you do with nuclear waste. ... My idea would be that you choose a site which is geologically stable, you sink a shaft and you bury it. Perhaps that is simplistic, I do not know."

Dr. Gribbin's comments reveal his ignorance not only about waste management in Australia (and generally) but also his ignorance about the most basic aspects of the uranium fission process, which yields far greater radioactivity than fresh fuel or uranium ore.

Dr. Gribbin's ignorance is all the more problematic given his assertion that "most objections to the nuclear reaction (sic) are based on lack of knowledge and irrational fear" and his belief that the "national interest" issue is based on "emotive, fear-inspiring expressions ... being misused in an attempt to associate the supply of medical radioisotopes from a small Australian reactor with atomic explosions, reactor meltdowns and nuclear war."

Likewise Dr. Barry Chatterton, representing the ANZAPNM, knows nothing about the radioactive waste problems (Senate Economics References Committee, 16/4/98 public hearing): "Obviously waste is an issue. The research reactor fortunately produces little waste. I think, again, that the waste of the last 40 years is currently being stored. Again, waste disposal is not particularly my area of expertise. I think it is an issue, but I believe that the present arrangements are satisfactory, certainly for the next 40 years."

Dr. Chatterton's ignorance was all the more problematic because the written submission from the ANZAPNM to the Senate Economics References Committee asserted that the issues raised by the 1993 Research Reactor Review - including waste issues - had been satisfactorily addressed.

The ANZSNM says 95% of nuclear medicine studies use Tc-99m. The figure is more like 70-80%, with 20-25% of nuclear medicine procedures using cyclotron-produced radioisotopes (25% according to ANSTO) and the remaining 5-10% of procedures using reactor produced isotopes other than Tc-99m. Why the ANZSNM would want to overstate the importance of Tc-99m is unclear. Such a manoeuvre certainly does little to support the case for a new reactor, since Mo-99m can certainly be imported and accelerator and/or spallation production may be viable on a commercial scale in the coming years.

The ANZSNM makes much of the employment generated by ANSTO, but on the same page says that the construction of 12 cyclotrons would "impact socially and politically in the areas surrounding each site". Is the imputation that the social and political impacts would be negative? Why is no mention made of the employment opportunities that would arise from further investment in cyclotrons? Why is no mention made of the "social and political impact" of building a new reactor? Such statements confirm the bias of the ANZSNM.

The ANZSNM parrots the claim made by the ANZAPNM that 12 cyclotrons would be needed to supply Australia's demand for Tc-99m. This issue is taken up in my response to the ANZAPNM submission.

The ANZSNM implies that all of Australia's Mo-99/Tc-99m comes from Lucas Heights. This is not true. Some Mo-99/Tc-99m generators are supplied by Amersham. I am told by one nuclear medicine specialist that the Amersham generator is easier to use, the product is superior to ANSTO's (higher specific activity), cost is comparable per unit radioactivity, and he "occasionally" experiences delays from both suppliers. If not for the heavy subsidisation of ARI by ANSTO (and thus tax payers), Amersham would undoubtedly increase its market share.

The ANZSNM claims that any delay in the project to replace HIFAR will result in disruptions to radionuclide supply. This is scare-mongering. As the ANZSNM well knows, if there is a lag between the closure of HIFAR and the start-up of a new reactor (or non-reactor accelerator and spallation alternatives), radioisotopes will be supplied from i) cyclotrons in Melbourne and Sydney (and other cyclotrons will be operating in Australia by the year 2005) and ii) overseas suppliers. Indeed supply from domestic cyclotrons and overseas reactors is a viable option for the medium to long term: my only objection to this is the ethical argument that we should not rely indefinitely on overseas countries to operate reactors and to deal with the attendant problems such as radioactive waste.

The ANZSNM mentions Australia's "international reputation" in nuclear medicine. One wonders if Australia has an international reputation at all in nuclear medicine, good or bad. A 1993 study reveals that ANSTO's contribution to Science Citation Index publications from 1981-1990 in the field of Radiology & Nuclear Medicine was 0.1% (Bourke and Butler, 1993). ANSTO accounted for 15.3% of all Australian contributions; therefore all Australian contributions accounted for approximately 0.6% of the world total. I am told by an ANSTO employee (who was perhaps exaggerating to make the point) that all of ANSTO's radiopharmaceutical research is "me-too" research, mimicking overseas research. Even Sm-153-based Quadramet, ANSTO's "gee-whiz" story for 1997 (along with the dating of a prehistoric Madagascan Elephant Bird's egg), is manufactured under licence from Dow Chemical.

The ANZSNM submission does not even address the option of greater reliance on imported isotopes. This is an extraordinary oversight. Has this topic been overlooked because the prospects for greater reliance on imports are - by any objective measure - very good? No-one disputes that there is now a glut on the world market, and will be for several decades to come given the Canadian venture in particular. Even ANSTO acknowledges that "many" radioisotopes can indeed be imported.

Further evidence of the bias of the ANZAPNM is that there is no mention whatsoever of most of the problems associated with the operation of a research reactor, such as radioactive waste (much of which arises from isotope production and processing).

The ANZSNM concludes that "The new reactor is essential to provide current and future demand for radionuclides." This is an erroneous conclusion from an ultra-flimsy submission from an organisation with a vested interest in a new reactor.

ANZSNM SUBMISSION NO. 8: APPENDIX BY DR. STEPHEN MEIKLE.

This appendix deals specifically with accelerator and spallation methods of Mo-99/Tc-99m production.

Dr. Meikle says "the ADONIS project remains in the concept stage and such a high energy cyclotron has not yet been constructed." Several comments need to be made in response:
- as for the claim that "such a high energy cyclotron has not yet been constructed", SCK-CEN says this cyclotron is based on today's fully-reliable commercial technology and can be upgraded within the next few years to a new 250-350 MeV, 5-10 mA cyclotron reference design.
- existing cyclotrons plus imports will suffice until spallation technology is fully developed.
- a number of spallation sources are already in operation around the world, used for scientific research.
- spallation production of radioisotopes (other than Mo-99/Tc-99m) dates from 1974: "The US Department of Energy (DOE) has been at the forefront of radioisotope production using spallation reactions since it initiated a program in 1974. High-current accelerators have been used to produce about 75 neutron-deficient radioisotopes using spallation targets. The accelerators are located at the Los Alamos National Laboratory and the Brookhaven National Laboratory. Research isotopes are also recovered from targets irradiated at the TRIUMF facility in British Columbia, Canada. The radioisotopes recovered are distributed for worldwide use in nuclear medicine, environmental research, physics research and industry. Products include Sr-82, Cu-67 (from ZnO targets), Ge-68, and some unique isotopes in quantities not available from other sources such as Be-10, Al-26, Mg-28, Si-32, Ti-44, Fe-52, Gd-148, and Hg-194." (For more information, see Jamriski, D.J., Peterson, E.J., and Carty, J., 1997, "Spallation Production of Neutron Deficient Radioisotopes in North America", Proceedings of the Second International Conference on Isotopes, 12-16 October 1997, Sutherland, NSW: Australian Nuclear Association.)
- in the same paragraph, Dr. Meikle discusses proton-induced fission of enriched Mo-100 (low yields, difficulty recovering Mo-100 for re-use) and the Adonis project. However they are separate projects. Yield is unlikely to be problematic for Adonis. Indeed SCK-CEN claims that one Adonis system could produce the entire of world demand for Mo-99. Nor is recovery of Mo-100 an issue for Adonis, since it does not involve Mo-100.

Dr. Meikle then turns to Tc-99m production using enriched Mo-100 targets in a medium energy cyclotron. He makes a number of unremarkable points:
- further work is required to verify the yields, specific activity and radionuclidic purity of the Tc-99m thus produced, under large-scale production conditions.
- specific activity is a very important parameter.

Dr. Meikle then acknowledges that published data (from Dr Lagunas-Solar et al.) indicates that the presence of unwanted isotopes of Tc are negligibly small. This too would be an unremarkable point, except that other advocates of a new reactor deny that a very high level of purity has been achieved. As Dr. Meikle also says, this has positive consequences for image quality.

Dr. Meikle's comments regarding logistics of supply of Tc-99m must be challenged. He says cyclotrons would be required on both east and west coasts of Australia, ideally one in each capital city. Even in the latter scenario, Dr. Meikle claims that cyclotrons could not supply Tc-99m for non-metropolitan areas given the 6 hour half life. This is a very dubious claim. Dr. Lagunas-Solar provides the following examples by way of comparison:
- iodine-123 (half life 13.2 hours) - produced in the USA and shipped throughout the USA and to Europe with 95% reliability.
- FDG (half life 2 hours) - transported 450 miles by air (3-4 hour delivery time).

Surely Tc-99m can be used to supply non-metropolitan areas if FDG - with a much shorter half life - can be transported 450 miles.

It must also be remembered that ANSTO's own data shows that 85% of nuclear medicine procedures in Australian are carried out in the eastern mainland states/territories (ANSTO, 1993, RRR Submission). The remaining 15% (in the SA, WA, NT and Tasmania) can be supplied as follows:
- for SA and WA, cyclotrons may be viable, or generators can be imported, or there may still be some generator manufacture (e.g. by ANSTO/ARI) using imported bulk Mo-99, or for SA supply from Melbourne may be viable.
- Tasmania can be supplied from Melbourne, or import generators.
- nuclear medicine is virtually non-existent in the NT; supply with generators would probably be the logical option.

Regarding scheduled and unscheduled maintenance, and the need for back-up supplies, such back-up can be provided by:
- cyclotrons in other cities/regions (e.g. Sydney to Melbourne); such supply regimes may not be ideal as a first-line option but would certainly suffice as back-ups.
- in addition, there is always the option of importing generators (or bulk Mo-99) for back-up and/or for supply of regions beyond an instant Tc-99m service.

Dr. Meikle finishes by saying that technical and logistical obstacles need to be overcome before direct cyclotron production of Tc-99m can be considered as a viable alternative. I dispute that logistics is an issue. As for the technical obstacles, these will not be resolved by the wave of a magic wand: why is there no funding for this research in Australia? (Incidentally, I asked that question of ANSTO once, and one reason given in response was that the international supply situation has stabilised, which acknowledges by implication that importation is a viable option.)

The ANZAPNM notes the growth in the use of nuclear medicine without mention of the overuse of nuclear medicine - a topic of ongoing discussion in the nuclear medicine professional literature. The ANZAPNM refers to an article by Patton in Seminars in Nuclear Medicine, in which article the following comments are made:

"There are ...... pressures on the nuclear medicine physician ...... to do testing even when the patient's interests are not clearly served. Physicians are driven by a need to do more because of internal or external professional or economic pressures, the pressure to do something, the fear of criticism or even malpractice, a need to control the situation and be looked up to, a desire for more income, a desire to keep the patient occupied and prevent him/her from seeking help elsewhere, scientific curiosity, a need to strengthen professional ties with colleagues doing tests, research interests, teaching interests, and other needs. ...... The nuclear physician may be under tremendous pressure from his hospital or his partnership to do more procedures to make his service more cost effective."

The ANZAPNM acknowledges that there have been "major advances in the other imaging modalities of CT scanning, ultrasound and spiral CT scanning" but claims that these advances have only improved anatomical imaging, not functional imaging (an area in which nuclear medicine is strong). This ignores competition in the realms of functional imaging. Magnetic resonance imaging (MRI) is primarily used to provide structural/anatomical information, but it has some applications in functional studies, such as in blood flow and metabolism studies and musculoskeletal pathology (Holman, 1994; Jacobson, 1994.). According to Dr. Holman, a nuclear medicine professional writing in The Journal of Nuclear Medicine, the axiom that radiology equals anatomy and nuclear medicine equals function is obsolete: radiology has historically been descriptive, non-quantitative, and structural, but that is changing "very fast" with functional radiology. A host of other diagnostic technologies are or can be used for functional diagnostics. Dr. Ell (1992) nominates the following technologies capable of providing localised biochemical information: nuclear medicine, microwave technology, infrared imaging, electronic spin resonance imaging, and MRI. The ANZAPNM refers to the article by Ell, and says that the above-mentioned techniques may have a few specific indications (i.e. they do not represent a major threat to nuclear medicine). This is a reasonable comment. It is also reasonable to note that nuclear medicine is under threat from a large number of alternative modalities. Collectively they could pose a threat to the future of nuclear medicine. Thus Jacobson notes that "The future holds the potential for many unpleasant battles between competing imaging specialists as the need to obtain the maximum information in the minimum time and at the lowest cost intensifies." A crucial point is that these issues are not just technical issues. They also have political and economic dimensions. Specifically, is there the political commitment to provide economic support for non-nuclear alternative imaging (and therapeutic) modalities, given that the alternatives offer advantages in areas such as radioactive waste. Patient management need not be compromised in such a scenario. It would simply mean providing funding for R&D projects in areas where alternatives potentially have equivalent or greater medical benefits.

Other modalities provide functional information for specific organs or physiological systems, such as echocardiology and computerised electroencephalography. There are also many chemical and biological alternatives to radioisotopes for in vitro diagnostic studies and research (Party and Gershey, 1995). One last, important point in relation to functional diagnostics is that positron imaging tomography (PET) is at the "cutting edge" in this field - as ANSTO acknowledges - and PET is largely reliant on cyclotron-produced radioisotopes rather than reactor products.

On another topic, the ANZAPNM indulges itself in a hypothetical exercise: what would happen if nuclear medicine studies were not available? Whoever suggested such a thing?! As the ANZAPNM is well aware, in the absence of a reactor, doctors will still have access to all of the commonly-used radioisotopes and literally dozens of others besides. This hypothetical exercise smacks of scare-mongering.

The ANZAPNM acknowledges the risk of radiation-induced iatrogenic (medicine-caused) cancer. The submission says: "The ANZAPNM agrees that 'it is both ethically and economically desirable to restrict the use of diagnostic radiation to only those who will benefit from it.' " This ignores the fundamental problem regarding overuse: in many cases it is economically desirable for doctors to use nuclear medicine in excess of medical need. Private practices which have made large investments in imaging equipment would be the sites of greatest concern. There is a considerable grey area with respect to justifiable use. The ANZAPNM appears to suggest that overuse is not a "major problem" because of the high level of training of nuclear medicine specialists and the because all patients are referred from other medical practitioners. This ignores the problems listed above in the quote from Dr. Patton. The extent of overuse is open for debate. While the ANZAPNM appears to believe it is not a major problem, others in the field are more concerned. For example Dr. Derek Roebuck, a radiologist writing in the Medical Journal of Australia, argues that the risk of causing malignant tumours through diagnostic tests involving ionising radiation - especially nuclear medicine, x-radiology, and computerised tomography - is widely underestimated, and that many new tests have been introduced without clear evidence of their net benefit to patients or their comparative advantage over alternative tests, and without precise evaluation of the radiation dose delivered.

The ANZAPNM says that "Cost benefit analyses are in a rudimentary stage of development in all medical fields, not just nuclear medicine." Indeed. Extravagant, overblown claims about the value of a range of all medical technologies must be resisted, as must extravagant, overblown claims about the value of nuclear medicine (which are commonplace). While on the cost-benefit issue, it is worth reiterating that Dr. Khafagi, a nuclear medicine specialist who doubles as a member of the ANSTO Board, is on record in a 1992 journal article saying that "our current information on cost is somewhat limited, if not arbitrary, and thorough evaluation of the only meaningful end-point - patient outcome - is scanty."

The ANZAPNM notes that Medicare rebates for (cyclotron-based) PET will depend on the outcome of a comprehensive evaluation. If only the same could be said of reactor-based radioisotope techniques (and many other areas of medicine for that matter).

Importation:
- the ANZAPNM says that Mallinckrodt's facility in the Netherlands is still to be completed. My understanding is that the plant (reactor plus processing facilities) is already operating and has been for some years. I am told by an American scientist who visited the plant that it can produce 20 000 Ci/week of Mo-99, which is greater than world demand.
- the ANZAPNM says the two dedicated radioisotope-production reactors in Canada have not yet been built, but my understanding is that the first of these reactors will be operating soon if indeed it is not already operating.
- it appears from the above two points that the ANZAPNM is trying to create the impression that the global supply situation is still tenuous. This is false.
- the ANZAPNM points to the US DOE's project to convert a reactor for Mo-99 production. However, the three major radiopharmaceutical companies which supply the American market all lost interest in the DOE's Mo-99 project several years ago and pursued foreign supply sources. None of these companies has committed to purchasing Mo-99 from the Sandia Laboratory. I am told by an American nuclear medicine researcher that there is a widespread view in the nuclear medicine community that the project should not proceed and that the money would be better spent on different projects. Moreover the DOE insists that the Sandia reactor will only be used as a back-up source, and that federal government support for the project will end when American, Canadian, or other suppliers establish new, reliable sources. Thus the facility is likely to be closed when the new Canadian reactors are operating. The American situation is evidence of the increasingly globalised nature of the radiopharmaceutical industry, not of the need for a domestic reactor.
- the ANZAPNM expresses concern about restrictions on the maximum amount of radioactivity that can be imported legally and safely. The maximum radioactivity allowed is known as the Transportation Index or TI. But as the ANZAPNM would be well aware, other countries import large quantities of radioisotopes. For example the USA and Japan have relied on Canada for their entire supply of Mo-99 for some years. The volumes involved vastly exceed Australian demand - to give some indication, American demand is roughly 40% of world demand, compared to about 1% for Australia. TIs for Mo/Tc generators vary depending on the shielding. For example small 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 actually much lower (despite the enclosed radioactivity being higher), ranging from 0.8 to 1.2. Amersham's largest generator is 100 GBq which, due to different reference dates, is equivalent to ANSTO's 120 GBq.
- generator importation is but one option - it might be appropriate if, for example, most of Australian demand is met by cyclotrons producing direct Tc-99m and a few generators must be imported to supply distant markets. But if Mo-99/Tc-99m is to be imported, the simplest option after the closure of HIFAR will be to import bulk Mo-99 with generator manufacture at ANSTO (or possibly central radiopharmacies converting bulk Mo-99 into unit-dose Tc-99m radiopharmaceuticals which are then supplied to hospitals). ANSTO imports bulk Mo-99 when HIFAR is shut down. ANSTO say they use a number of suppliers (proof positive that the near-monopoly position of Nordion in the early 1990s is a thing of the past). Bulk Mo-99 is very well shielded in DU so the TI is not much of a problem if a problem at all. TI limits per aircraft vary. For British Airways the limit on 747-400 aircraft is 32. For Cathay Pacific, it is 28. For Singapore Airlines, it is 24.
- many radiopharmaceuticals require non-radioactive cold kits as well as the radioactive isotope. Cold kits are available from ANSTO's competitors, usually on a next-day basis. ANSTO can do no better.
- more generally on the above points, the ANZAPNM (and others) are constantly finding new arguments against importation and the arguments are always flawed. If importation was a particularly difficult, unsatisfactory or expensive proposition, then it would not be the case that over 75% of nuclear medicine procedures all around the world use imported radioisotopes; it would not be the case that for every two countries that have chosen to build a research reactor (usually from the 1950s to early 1970s) there are five countries that have chosen not to build a research reactor; it would not be the case that advanced industrial countries such as the USA, the UK and Japan rely so heavily on imports plus domestic cyclotrons. The Research Reactor Review (1993, p.224) noted that countries importing radioisotopes had either overcome logistical problems with importation, or found them not to be a problem in the first place.
- the ANZAPNM refers to costs, but only mentions an indium-111 radiopharmaceutical. Amersham has a monopoly on sales of this product - there is no comparison to be made with local and domestic sales. It might be argued that the high price of this monopoly product lends weight to the argument that the prices of imported products might rise in the absence of a domestic competitor. But for monopoly products such as the indium-111 compound (and I understand strontium-89 Metastron also fits this category), the issue of a domestic reactor is neither here nor there anyway. To take a much more important example, three or more overseas companies can supply Australia with gallium-67 and thallium-201 (both cyclotron produced, the second and third most commonly-used radioisotopes in nuclear medicine after Tc-99m). This illustrates the point that for many radioisotopes, there will be plenty of competition regardless of whether there is domestic production in Australia. To take Mo-99 - the most important example because it is the most commonly-used isotope and because current production uses reactors - in the absence of a domestic reactor there are approximately 5-7 alternative suppliers! (South Africa AEC, USA/DOE, Canada/Nordion, Netherlands/Mallinckrodt, Belgium/IRE, I understand Mo-99 production has begun in South Korea/KAERI, possibly Indonesia/BATAN, etc.)
- a straight comparison of imported vs. domestic costs is not possible because ANSTO/ARI refuses to provide cost data (whereas Amersham has supplied its price-list). In any case such a comparison would be meaningless unless it factored in the large subsidisation of ARI by ANSTO (and thus tax payers). The marginal fee charged to ARI by ANSTO does not include any component for reactor capital costs, decommissioning costs, waste management costs etc.
- the ANZAPNM mentions time delays. What little hard data is available suggests this is, at most, a marginal issue. The South African Atomic Energy Corporation (SAAEC), which supplies Mo-99 during HIFAR shut-downs, claims 99.5% reliability. I have asked ANSTO repeatedly if it disputes the SAAEC's claim and ANSTO does not respond. Even in response to a parliamentary Question on Notice, ANSTO dodges this issue. A Western Australian doctor tells me he "occasionally" experiences delays with imported generators from Amersham (UK) and ANSTO/ARI. I am told that supply from Canada to Japan is rarely disrupted. Reliability of supply is rarely if ever discussed in the nuclear medicine journals.
- the ANZAPNM mentions R&D, euphemistically noting that R&D in Australia is "young and evolving". The simple solution is to put more effort into accelerator and/or spallation R&D. The past decade suggests that little will be lost in terms of reactor-based medical R&D. About five years ago we were told that dysprosium would completely replace yttrium-90, but dysprosium still has not been released. I am told that ANSTO's neutron activation program for research into protein loss "fell over" a few years ago. With or without a new reactor, ANSTO's contribution to the development of new products will be negligible, because overseas operations, especially in the USA and Europe, have vastly greater resources for R&D (data on this available on request). I am told by an ANSTO employee (who was perhaps exaggerating to make the point) that all of ANSTO's radiopharmaceutical research is "me-too" research, mimicking overseas research. A former ANSTO employee confirms the above comment and adds that it applies more broadly, not just to medical research. A nuclear medicine researcher told me he was impressed that ANSTO had Sm-153 to market given ANSTO's history of incompetence in such matters!

Cyclotron production of Tc-99m.

The ANZAPNM draws from literature at the University of California Chemistry and Agriculture Program (UCCAP) internet site to contend that at least 12 cyclotrons would be needed. However in his most recent paper, Dr. Lagunas-Solar says: "By using high-intensity beams (i.e. 1 mA) available from modern H- accelerators, and by extracting multiple H+ beams to bombard enriched 100Mo targets, this method could provide nearly 851 GBq (23 Ci) of 99mTc in 1-h bombardments. Because of this large-batch potential, this new method appears to be an effective alternative to the production and distribution of 99Mo -> 99mTc generators."

With yields of 23 Ci from 1-hour bombardments, and Australian demand at 300 Ci, it seems unlikely that anything like 12 cyclotrons would be required.

Existing cyclotrons: The ANZAPNM says there appear to be logistical difficulties supplying regional facilities with FDG from the Sydney cyclotron. However it is drawing a long bow to then say, as the ANZAPNM does, that this raises concerns about supply of Tc-99m which has a 6-hour half life compared to 2 hours for FDG.

Issues raised by the RRR: The ANZAPNM asserts that issues raised by the RRR have been satisfactorily addressed - but without a word to justify the assertion! There is no indication whatsoever that the ANZAPNM is even aware of the issues raised by the RRR.

Further evidence of the bias of the ANZAPNM is that there is no mention whatsoever of most of the problems associated with the operation of a research reactor, such as radioactive waste (most of which arises from isotope production and processing).

Dr. Chatterton, representing the ANZAPNM, mentioned ANSTO's 1997 gee-whiz story, samarium-153 Quadramet in his verbal submission to the Inquiry. He says it has a palliative effect more quickly than Sm-153. True, but this is a marginal advantage: according to a 1997 article by Ben-Josef and Porter, in the Annals of Medicine, relief occurs about 7-14 days after treatment with Quadramet whereas strontium-89 chloride (Metastron, imported by Amersham) usually begins having a palliative effect about 10-20 days after administration. Moreover the short half life of Sm-153 is disadvantageous in that it is effective for a shorter time. According to the 1997 Annals of Medicine article, the median duration of palliation for Sm-153 Quadramet is 2.6 months whereas Sr-89 Metastron is effective for an average of six months (range 4-15 months). Dr. Chatterton's comment that Sm-153 causes less damage to other organs (compared to Sr-89 Metastron) is strongly contested by Amersham. Amersham says Sm-153 has a much higher bone marrow toxicity (compared to Sr-89 Metastron) and many physicians prefer to use Sr-89 Metastron in sicker patients because of its LACK of toxicity. Some Australian states require Sm-153 patients to be hospitalised because of the gamma emissions emanating from the patient. Sr-89 is a pure beta emitter and therefore creates no such problems for the safety of the general public. Therefore the patient leaves the hospital much quicker.

As with the ANZSNM submission, it can only be concluded that the ANZAPNM submission is flawed on numerous counts and reflects the commercial and/or career interests of ANZAPNM members.

Ell, P.J., 1992, "Challenges for nuclear medicine in the 1990s", Nuclear Medicine Communications, Vol.13, pp.65-75.

Holman, B. Leonard, 1994, "The Future of Nuclear Medicine: Autonomy or Integration? Integrating Nuclear Medicine with Radiology", The Journal of Nuclear Medicine, Vol.35(10), pp.27N-33N.

Jacobson, Arnold F., 1994, "Nuclear medicine and other radiologic imaging techniques: competitors or collaborators?", European Journal of Nuclear Medicine, Vol.21(12), pp.1369-1372.

Khafagi, F.A., 1992, "Economic Evaluation in Nuclear Medicine", ANZ Nuclear Medicine, June, pp.16-19.

Lagunas-Solar, Manuel C., and Zeng, Nolan X., "Accelerator Production of Technetium-99m as an Alternative to Reactor Methods", Submitted to ANZ Nuclear Medicine, 22 October 1997.

Party, E., and Gershey, E.L., 1995, "A Review of Some Available Radioactive and Non-Radioactive Substitutes for Use in Biomedical Research", Health Physics, Vol.69(1), pp.1-5.

Patton, Dennis D., 1993, "Cost-Effectiveness in Nuclear Medicine", Seminars in Nuclear Medicine, Vol.XXIII(1), pp.9-30.

Roebuck, Derek J., 1996, "Ionising radiation in diagnosis: do the risks outweigh the benefits?", Medical Journal of Australia, Vol.164, pp.743-747.