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Alternative Production Methods to Face Global Molybdenum-99 Supply Shortage

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Alternative Production Methods to Face Global Molybdenum-99 Supply Shortage Brief Review Article Alternative production methods to face global molybdenum-99 supply shortage Abstract The sleeping giant of molybdenum-99 (99Mo) production is grinding to a halt and the world is won- dering how this happened. Fewer than 10 reactors in the world are capable of producing radio nu- clides for medicine; approximately 50% of the world’s supply of raw material comes from National Research Universal (NRU) reactor in Canada. Many of these reactors, like the NRU, are old and aging. No one of these reactors, and probably not even all of them in combination, can replace the produc- tion of NRU. As the healthcare industry faces an aging population and the demand for diagnostic services using 99mΤc continues to rise, the need for a consistent, reliable supply of 99Mo has become increasingly important, so alternative methods to produce 99Mo or even directly 99mΤc had to be considered to avoid a supply shortage in the coming years. This need guides to the production of 99Mo by replacing the Highly Enriched Uranium (HEU) target in a nuclear reactor with Low Enriched Uranium (LEU) and furthermore to the use of accelerators for manufacturing 99Mo or for directly producing 99mTc. Hell J Nucl Med 2011; 14(1): 49-55 Published on line: 26 March 2011 Introduction olybdenum-99 (99Mo) is an isotope of the element molybdenum, a metal discov- ered in the 18th century and is produced using highly enriched uranium (HEU) M targets. Brookhaven reactor pioneered research using subatomic particles as tools to investigate the structure of matter. The Brookhaven High Flux Beam Reactor first achieved a self-sustaining chain reaction on October 31, 1965. For over 30 years, this reac- tor was one of the two premier beam reactors in the world, the other being the Institut Laue-Langevin reactor in Grenoble, France [1]. Nowadays 99Mo is produced in only six nuclear reactors in the world: High flux reactor (HFR) in The Netherlands, National Research Universal (NRU) in Canada, Belgium reactor (BR2), Safari1 in Africa, Osiris in France and Maria in Poland, two of which are considering to have highly uncertain production [2-3]. The location and the percent of the global market produced by each are as follows: Canada (33%), The Netherlands (32%), South Africa (15%), Belgium (6%) and France (6%) with others supplying the remaining 8%, mostly for national or regional consumption, as it is shown in Figure 1. The average age of these reactors is 47 years [4]. Concern is now mounting about the age, safety and reliability of these reactor operations following a series of well publicised technical problems and unscheduled plant shutdowns. New reactors are urgently needed to prevent future shortages of 99Mo, and hence technetium-99m (99mTc). On 17 February 2010, Covidien and the Institute of Atomic Energy in Poland have agreed to augment the global supply of 99Mo by adding the Poland’s Maria Research Reactor to the company’s supply chain. The reactor, located approximately 30km southeast of War- saw, first operated from 1975 until 1985 when it was taken off-line for a complete redesign and resumed normal operations in 1993. Maria is considered to be a relatively new reactor, with an operating life extending beyond 2020. The U.S. Food and Drug Administration (FDA) and Health Canada have approved (11 March 2010) the use of the Maria Research Reactor in Poland as a site to irradiate HEU targets for 99Mo production [5-6]. The raw material, which is produced in a nuclear reactor, is then transferred to a process- ing facility where it is purified through a multi-step process. The finished raw of 99Mo is sent to generator manufacturers to introduce them in medical markets (Fig.1) for use of its decay product 99mTc in medical applications. In 1959 the U.S. Brookhaven National Labora- tory (BNL) started to develop a generator to produce 99mTc from the reactor fissionable product 99Mo, which has a much longer half-life. The first 99mTc radiotracers were devel- oped at the University of Chicago in 1964. Between 1963 and 1966, the interest in 99mTc www.nuclmed.gr Hellenic Journal of Nuclear Medicine January - April 2011 Brief Review Article grew as its numerous applications, as a radiotracer and diag- tional Atomic Energy Agency (IAEA) attempts to monitor nostic tool, were described in publications. By 1966, BNL was and control enriched uranium supplies and processes in its unable to cope with the demand for 99Mo/99mTc generators efforts to ensure nuclear power generation safety. and withdrew from production and distribution, in favour of Low enriched uranium (LEU) is considered to be enhanced commercial generators. The first commercial generator was with less than 20% of 235U. Uranium enriched to three to five produced by Nuclear Consultants, Inc. of St. Louis, later taken per cent, for example, is used to fuel reactors that generate over by Mallinckrodt (Covidien), and Union Carbide Nuclear electricity. Fresh LEU used in research reactors is usually en- Corporation, New York [7]. riched 12% to 19.75% 235U. In the 1970s, recognizing the risks of nuclear proliferation and terrorism associated with civilian use of HEU, both the Reactors Markets U.S. and Soviet governments launched programs to facilitate the substitution of HEU by non-weapon-usable LEU, contain- NRU ing less than 20% 235U, for use HEU in civilian research-reactor N. America fuel and in radionuclide production targets. This program is now international [8, 9]. U.S.A Molybdenum-99 (99Mo) and some important medical iso- Maria topes can be produced either in a HEU or a LEU reactor. Europe 50% Molybdenum (42Mo) Molybdenum is a Group 6 chemical element with atomic HFR number 42. The name comes from Ancient Greek mόλυβδος Europe molybdos, meaning lead, since its ores were confused with lead ores. The free element is a silvery metal. It readily forms hard, stable carbides, and for this reason it is often used in BR2 Restrest Ofof world World high-strength steel alloys. Molybdenum does not occur Europe as the free metal in nature, but rather in various oxidation 50% states in minerals. Osiris Molybdenite is the principal ore from which molybdenum is now extracted and was previously known as molybden- Europe ite which was often implemented as it were graphite. Even when molybdena was distinguishable from graphite, it was still confused with a common lead ore, called galena. In Safari 1754, Molybdenite examination results showed that it did S. Africa not contain lead. Molybdenum was differentiated as a new entity from minerals salts of other metals in 1778. The metal 99 Figure 1. Current Mo suppliers in 2010. was first isolated in 1781. There are 35 known isotopes of molybdenum ranging in Uranium (92U) atomic mass from 83 to 117, as well as four metastable nu- Natural uranium found99 in the Earth’s crust consists almost clear isomers. Of the seven naturally occurring isotopes, only Figureentirely 1. ofCurrent 238U; only Moabout suppliers 0.7% is 235inU. 2010. Uranium-238 (238U) molybdenum-92 (92Mo) and molybdenum-100 (100Mo) are is the most common isotope of uranium found in nature. unstable and decay into isotopes of niobium, technetium It is not fissile, but is a fertile material: it can capture a slow and ruthenium. Molybdenum-98 (98Mo) is the most abun- Uraniumneutron (92U) and after two beta decays becomes fissile pluto- dant comprising 24.14% of all Mo. 238 99 nium-239. U is fissionable by fast neutrons, but cannot The production238 of Mo by neutron irradiation of targets Naturalsupport uranium a chain found reaction in the because Earth's inelasticcrust consists scattering almost re- entirelyof HEU of or of LEUU; only in a nuclear about reactor0.7% is is organized in terms of 9 235U. ducesUranium-238 neutron energy. (238U) Itis has the a mosthalf-life common of 4.468Χ10 isotope years, of uraniumthree processes. found in Fabrication nature. It of is uranium not targets, irradiation or 4.468 billion years radiates alpha-particles and decays of targets in a nuclear reactor and dissolution of the uranium fissile,into but 234 U,is whicha fertile has material:a half-life ofit 245,500can captu years.re aThe slow rela -neutrontarget, and recovery after and two purification beta decays of 99 Mo. The 99Mo is a par- tion between 238U and 234U gives an indication of the age of ent radioisotope to the short-lived gamma-emitting daugh- 238 becomessediments fissile thatplutonium-239. are between 100,000U is fissionable years and 1,200,000 by fast neutrons, ter radioisotope but cannot 99mTc, support the nuclear a chain isomer which 99mTc is used years in age. in nuclear medicine imaging [10-11]. 9 reactionHighly because enriching inelastic uranium scattering (HEU) includes reduces enough neutron 235 Uenergy. to It has a half-life of 4.468×10 235 99 years,maintain or 4.468 a chainbillion reaction. years radiatU nucleuses alpha-particles can release energy and decaysMo ininto medical 234U, applications which has a half- by splitting into smaller fragments, which then hit and split Technetium-99m is the most widely utilized radionuclide life ofother 245,500 235U atoms, years. and The so relation on. When between the 235U 238componentU and 234 isU givesin the anworld indication for molecular of the and age nuclear of diagnostic imaging enriched to 90% or more the atoms abide fission in the con- tests. At over 18.5 million doses, 99mTc accounts for 82% of sedimentstrolled that conditions are between of a nuclear 100,000 reactor. years HEU and is 1,200,000 also used inyears all in diagnostic age. radiopharmaceutical injections each year. This fast neutron reactors, whose cores require about 20%235 or isotope has a half-life of about 6 h235 and emits 140keV photons Highlymore enrichingof fissile uraniummaterial.
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