Last year a commission of experts has advised the government of Canada, one of the major medical isotopes producing nations, to invest in accelerators for the production of among others radioisotopes, currently made by research reactors.71 Though the expert panel kept the option open to build a new research reactor, the Canadian government decided to cancel this option based on good arguments: “From a purely isotope perspective, outside the considerations of the other missions of a research reactor, the Government finds that the very high costs and very long lead times make this a less attractive option than others. Based on the experience of other countries, it would likely take a decade or more to bring a new research reactor on stream. Also, the significant fixed costs and production capacity would be disproportionate to Canada’s isotope needs and could not be recouped from the market. Waste liabilities associated with long-term reactor-based isotope production would be significant and again difficult to fully recover.” [..] “A research reactor is only one piece of the linear supply chain that exists today. Replacing one piece of a linear supply chain, such as simply replacing the NRU with another reactor, would do little to develop the diversity and redundancy that the Panel believed were critical for ensuring security of supply. The lesson learned is that more should be done to create cross-linked and distributed supply chains that are not as vulnerable to single-point failures. An announcement that a new research reactor would be built in Canada to produce medical isotopes would discourage investment in alternative sources of supply, both in Canada and in other countries. The supply chain would continue to remain vulnerable to the single-point-of-failure problem that exists today, and generators would likely be manufactured outside of Canada.”72
Such a decision had to come to this in the end. The long history of choosing primarily research reactors for isotopes production has miserably failed. The continued disruptions in the supply of radiopharmaceuticals are the result of making wrong decisions. The development of the Maple-reactors in Canada is a perfect example to show the far-reaching consequences of such policy.
5.1 The MAPLE failure
In the mid 1990s the Canadian producer of radioisotopes MDS Nordion commissioned Atomic Energy of Canada Limited (AECL) to build two nuclear reactors. The two research reactors were named to the project name under which they were built: Multipurpose Applied Physics Lattice Experiment (MAPLE). Both reactors, Maple 1 and Maple 2, were especially designed for the production of molybdenum-99 (99Mo). Each of these reactors was to have the capacity to meet the world’s 99Mo needs, so that each would serve as a backup for the other. With the prospect of the Maple reactors entering service in early 2000, the development of alternative production methods for 99Mo or 99mTc never reached maturity. And meanwhile, after more than ten lost years for the development of cyclotron-produced isotopes, AECL cancelled the Maple Project in May 2008. The Canadian Nuclear Safety Commission (CNSC) denied a license to operate the Maple reactors due to a design fault. In 1996, MDS Nordion agreed with AECL to pay US$140 million for the design, development and the construction of the two new reactors. In 2005, five years after the reactors had to be delivered, these costs were more than doubled (US$330 million) without the prospect that they will entering in service. Canadian radio-isotopes are therefore still produced with the aged National Research Universal (NRU) reactor of which the current license expires in October 2011.73 Meanwhile the construction the new research reactor in the Netherlands will start within a few months. The total costs are projected on €500 million and the reactor has to be operable from 2018.74
5.2 Medical isotopes production is currently depending on five rickety reactors
Currently, around 95% of the worldwide medical reactor-produced isotopes are made with five aged research reactors in Belgium, Canada, France, The Netherlands and South-Africa which are frequently shut down for a longer period of time. The Canadian NRU reactor and the Dutch HFR together supply for about 80% in the worldwide demand of 99Mo, of which 60% is delivered by MDS Nordion (Canada) and the remaining part by Covidien Mallinckrodt
(The Netherlands). The other three reactors supply Europe and parts of Asia and also serve as back-ups when one of the large producers break down because of maintenance. All these reactors are 43 to 52 years old (mid 2010). The life span extension of the reactors cause - and will inevitably remain to cause –problems due to age. The problems are not associated with the reactors themselves but with the infrastructure: leaking containment vessels and leaking pipes buried deep in shielding walls. Such problems are difficult to isolate and solve, resulting in prolonged shutdowns. The smaller reactors could increase their production capacity, such as the much named Maria research reactor in Poland (more than 35 years old), but none of these reactors has the capacity of the HFR or the NRU to take over the production rate of radioisotopes. The announcement of France to postpone major repairs to the OSIRIS planned in 2010, because of the shutdowns of the NRU [May 2009 until August 2010(?)] and the HFR [February 2010 until August 2010(?)] will not bring any relieve in the continuing severe medical isotope shortages. Radioisotopes production with these wobbly nuclear reactors has been appeared very uncertain in the past years.75
Currently, around 95% of the worldwide medical reactor-produced isotopes are made with five aged research reactors in Belgium, Canada, France, The Netherlands and South-Africa which are frequently shut down for a longer period of time. The Canadian NRU reactor and the Dutch HFR together supply for about 80% in the worldwide demand of 99Mo, of which 60% is delivered by MDS Nordion (Canada) and the remaining part by Covidien Mallinckrodt
(The Netherlands). The other three reactors supply Europe and parts of Asia and also serve as back-ups when one of the large producers break down because of maintenance. All these reactors are 43 to 52 years old (mid 2010). The life span extension of the reactors cause - and will inevitably remain to cause –problems due to age. The problems are not associated with the reactors themselves but with the infrastructure: leaking containment vessels and leaking pipes buried deep in shielding walls. Such problems are difficult to isolate and solve, resulting in prolonged shutdowns. The smaller reactors could increase their production capacity, such as the much named Maria research reactor in Poland (more than 35 years old), but none of these reactors has the capacity of the HFR or the NRU to take over the production rate of radioisotopes. The announcement of France to postpone major repairs to the OSIRIS planned in 2010, because of the shutdowns of the NRU [May 2009 until August 2010(?)] and the HFR [February 2010 until August 2010(?)] will not bring any relieve in the continuing severe medical isotope shortages. Radioisotopes production with these wobbly nuclear reactors has been appeared very uncertain in the past years.75
5.3 Can Pallas overcome the acute shortage of medical radioisotopes?
The current High Flux Reactor in Petten, The Netherlands, will be replaced by the Pallas. This new research reactor has to enter service in 2018. This means under the most favorable conditions, because there are normally years of delays in the construction of nuclear reactors. Considering the highly uncertain production of the NRU (permanently shut-down in 2011) and the HFR, Pallas offers no solution for a safe and secure supply of technetium-99m in the short term. Also the French Osiris reactor will shut down for a longer period by the end of 2010 or in 2011, the permanent shut-down is in 2015. Possibly Australian and German research reactors can take over a part of the production, however, as said before this will never be sufficient to keep up the supply of medical isotopes.
The recent decision of the Canadian government to cancel the construction of a new research reactor and to invest in the production of cyclotron-based radioisotopes have to be seen against this background. Hopefully this will be the first step in the revival of the original radioisotopes production methods: the charged particle accelerators. The development of a proton-induced neutron accelerator or the accelerator driven system (ADS), a sub-critical assembly driven by an accelerator, shows promising results. Such systems can be used until alternative medical isotopes produced by accelerators will arrive on the market. AMIC, a US company, in conjunction with researchers from a number of U.S. universities has tested ADS successfully for the production of molybdenum-99 and expects to start production in the nearby future to cover the US demand for technetium.76 ADS is also a good alternative for the production of yttrium-90 (90Y), holmium-166 (166Ho), erbium-169 (169Er), and iodine-125 (125I), projected to be produced by Pallas.
71 Report of the Canadian Expert Review Panel on Medical Isotope Production, 30 November 2009. http://nrcan.gc.ca/eneene/sources/uranuc/pdf/panrep-rapexp-eng.pdf
http://nrcan.gc.ca/eneene/sources/uranuc/mediso-eng.php
72 Government of Canada Response to the Report of the Expert Review Panel on Medical Isotope Production. March 31, 2010
http://nrcan.gc.ca/eneene/sources/uranuc/pdf/isotopes-gc-re-eng.pdf
73 NTI - Canada, Updated May 2009 http://www.nti.org/db/heu/canada.html New Scientist 19 Jan 2010; Nuclear safety: When positive is negative http://www.newscientist.com/article/mg20527431.400-nuclear-safety-when-p...
74 Bouw Pallas kernreactor vertraagd http://www.rtvnh.nl/nieuws/index.asp?newsid=106000
75 Ruth, Thomas J.; The Medical Isotope Shortage: http://www.aps.org/units/fps/newsletters/200910/ruth.cfm
76 Globe Newswire, 3 Nov 2009: Advanced Medical Isotope Corporation Receives Positive Results from Initial Tests of a Proprietary and Innovative Method for the Domestic Production of Molybdenum-99 http://www.globenewswire.com/news.html?d=177328