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Technetium-99m

Technetium

Medicine

5th Int. Particle Accelerator Conf. (IPAC'14), Dresden, Germany, June 15-20, 2014

Recent and ongoing shortages in reactor-based supplies of molybdenum-99 for hospital production of the important medical radioisotope Technetium-99m have prompted the re-examination of the alternative production methods using conventional and laser-based particle accelerators. At present the UK has no domestic source of molybdenum99 and relies exclusively on overseas supply; the National Health Service, with professional partners, is therefore examining the options for domestic production of molybdenum-99 and/or technetium-99m to increase security of supply. In this paper we review the acceleratorbased methods from a UK perspective, and outline the most promising methods for shortand medium-term supply, which include low-energy cyclotron and photonuclear reaction routes using enriched Molybdenum-100 targets. THE MOLYBDENUM SUPPLY CRISIS Technetium-99m (Tc) is the most widely used radioisotope in nuclear medicine today, and accounts for over 80% of the present 3.2 billion dollar global market in radiopharmaceuticals; Fluorine-18 products for positron emission tomography (PET) account for most of the rest [1]. Tc is favoured due to its single 140 keV emission during decay, its short half-life of 6 hrs that minimise patient dose during imaging, and its normal production route whereby its Mo precursor is distributed to hospitals in a generator which is then eluted to obtain the Tc built up from the Mo decay (Mo half life is 66 hrs). Mo is today primarily obtained via fission of HEU targets each irradiated for several days in one of several ageing research reactors, and a crisis is looming due to the foreseen shutdown of one of the largest production facilities at Chalk River in Canada; the NRU reactor there provides nearly 50% of the global weekly supply of 12,000 6-day Curies of Mo, ∗ Work supported by STFC grant ST/G004277/1 † hywel.owen@manchester.ac.uk and after its shutdown in 2016 demand will outstrip supply by some margin [2–5]. More than 30M procedures are delivered each year (53% North America, 23% Europe, 20% Asia, 4% Rest of World), and whilst the nuclear medicine community is examining alternative imaging methods it is likely that Tc provisionwill be needed for at least twenty years; global demand is set to rise by between 1% and 2% per annum over that period. For example, the UK presently administers around 0.5M Tc procedures each year [1], and whilst PET, CT and MRI could replace Tc for some indications this would impact existing capacity of those alternative techniques to meet the needs of other imaging procedures. Use of some of these alternatives also incur greater patient radiation dose; the short Tc half life and pure gamma emission means a typical administered dose of up to 27 mCi (1000 MBq) incurs a patient dose of around 24 mSv. Previous unplanned outages of the NRU and HFR Petten reactors in 2009/2010 resulted in optimised usage of Tc such that demand reduced to around 10,000 6-day Curies per week; further optimisation could be achieved via changes such as weekend processing of Mo to avoid loss of activity through decay [6]. As well as facing the global fragility of sourcing supply, the UK has the additional problem that it has no suitable high-flux research reactors and therefore no present domestic source either of Mo or directly of Tc, although it does have a large generator manufacturing plant at Amersham; interruption to the required weekly supply of Mo generators could leave the UK with no supply at all. Other factors include the likely US restriction on HEU shipments after 2020, and uncertainties as to when replacement European reactors become available (such as the Jules-Horowitz reactor currently under construction). Because of these issues, a national working group has been set up to examine how to obtain a more secure source of Tc for domestic use. Even with the introduction of full cost recovery at the nuclear reactor [7] it is unlikely that a commercial provider will build a UK-based reactor that processes Mo, and in Proceedings of IPAC2014, Dresden, Germany THOAB02 08 Applications of Accelerators U01 Medical Applications ISBN 978-3-95450-132-8 2815 C op yr ig ht © 20 14 C C -B Y3. 0 an d by th e re sp ec tiv e au th or s common with other countries the UK is therefore examining non-reactor approaches that utilise accelerator bombardment of targets. ACCELERATOR-BASED APPROACHES Similar to many other countries, Tc is presently mainly provided in the UK by processors utilising fission Mo from the SAFARI, HFR and OSIRIS reactors; around 100 radiopharmacies receive generatorswhich are then used in around 200 nuclear medicine departments [1]. Centralised production using accelerators is possible in principle but as yet no mechanism exists to bring this about; alternative methods must consider differences in issues such as specific activity, dose preparation and licensing of radiopharmaceuticals. A number of technical approaches are possible [8–10], which broadly divide into fission-based and transmutation-based methods; the four most prominent methods are now described. Accelerator Fission Production Photofission production of Mo is most likely best achieved using a combination of a convertor target (e.g. W or Ta producing c.15 MeV γ-rays from c.30-50 MeV electrons) and a solid production target of depleted U, LEU or HEU [4, 9, 11]. Lower enrichment reduces licensing and proliferation issues, but use of uranium targets requires similar hot-cell processing and waste disposal to reactor Mo production. Nevertheless, a single c.100 kW accelerator facility could provide sufficient Mo for the UK [12], and suitable superconducting cavity technology has been developed at Daresbury Laboratory (and elsewhere) from which such an accelerator could be constructed [13]. An alternative is to use neutron-based fission in a subcritical assembly, utilising U either in solid or liquid form; the best-developed approach is SHINE, wherein photoneutrons drive fission in a reflected subcritical LEU solution in heavy water [14]. The disadvantage of subcritical systems is the relative difficulty in their licensing.

Options for UK Technetium-99m Production using Accelerators