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| Fig. 1: The first Technetium-99m generator shown without shielding after its discovery at the Brookhaven National Laboratory in 1958. (Courtesy of the DOE. Source: Wikimedia Commons) |
Nuclear Medicine is based in the widespread use of radioisotopes for various therapeutic purposes. Since their initial discovery, radionuclides have widely been used in the field of medicine.
The development of the first cyclotron by E. Lawrence in 1930 at Berkeley created the ability to produce usable quantities of radionuclides, advancing the field of nuclear medicine. By the end of 1933 Lawrence had created a machine that was able to generate a beam of 3 MeV deuterons with an intensity equivalent to large quantities of radium in a Radium- Beryllium source. [1] The ability to produce these radionuclides (initially via the cyclotron,) paved the way for a new type of pharmaceutical that would utilize nuclear chemistry to achieve therapeutic treatment.
Radioisotopes are unstable chemical elements that undergo radioactive decay during which they emit excess energy in the form of radiation, often in the form of gamma rays. Gamma rays are high enough in energy that they are able to penetrate the body, allowing these radioisotopes to be essential tools used in nuclear medicine, where they are often combined with a drug that's able to target a specific area of the body and guide the radioisotope there. [2]
With the discovery of the technetium-99m (Tc-99m) generator, users could extract Tc-99m from its "mother" isotope Mo-99. Molybdenum-99's half-life allows for it to be transported over longer distances and thus be more accessible for hospitals to use in order to extract the Tc-99m. This procedure, in combination with the relatively simplistic methods for production of radiopharmaceuticals, helped to make nuclear medicine more widely available even for small hospitals. [1] Fig. 1 shows what the generator initially looked like upon its creation.
Beginning in the 1950s, pharmaceuticals that were radioactively labeled allowed for the study of internal organs such as the kidneys, heart, and liver, which was more easily done through simple radioisotope production in the hospital. [1] The rapid increase in generation and availability of radionuclides in medicine immediately created an economical opportunity worldwide. Soon after their initial use in medicine, the economical market surrounding radioisotopes began to grow.
In order to understand the impact of medical radioisotopes on the economy, it is important to first understand the way in which the most prominent isotope used in medicine is produced.
As previously stated, this widely used radioisotope is Tc-99m due to its short half life and abundance in supply. This radioisotope accounts for over 80% of diagnostic nuclear medicine procedures. A key part of Tc-99m production is carried out in a small number of nuclear research reactors. This radioisotope is produced by the radioactive decay of Mo-99, which is currently achieved in nuclear research reactors through the fission (splitting) of enriched uranium. Neither isotope can be stocked in large quantities because they decay rapidly since the half-life of Tc-99m is 6 hours and the half-life of Mo-99 is 66 hours. [2]
In 2009, the temporary shutdown of two reactors caused a global shortage of Tc-99m. This led to great complication of planned medical procedures as well as disrupting research globally. In 2015 and 2016, two of the largest reactors producing medical radioisotopes were closed, prompting concerns over future shortages. [2] The year period between 2009 and 2010 resulted in a decrease of supply of these radioisotopes and thus an increase in their prices during this time as well.
Since that point in time many industries and governments have created task forces to determine how to avoid a shortage problem in the future. An example is the Nuclear Energy Agency (NEA) and its High-level Group on the Security of Supply of Medical Radioisotopes (HLG-MR) who examined the causes of supply shortages and developed a policy approach, including principles and supporting recommendations to address those causes. [2]
The molybdenum/technetium supply chain is very complex and faces a number of significant challenges, both short and long term. A large factor in the supply chain is the requirement of getting the product to the patient while minimizing radioactive decay and potential losses to its economic value. This factor is due to the short half-lives of the radioisotopes. The complete process from production to consumption of Tc-99m must move very quickly and predictably to get the product delivered to the consumer (patient).
Overall, the effect of these poor economic conditions is that the Mo-99 supply chain currently relies on older reactors. There are five reactors globally from which Mo-99 is generated. One of these is in Chalk River, Ontario, where the Mo-99 is produced before processing. [3] This National Research Universal (NRU) reactor has been operational for more than 50 years. It was expected to be replaced with 2 new reactors, called MAPLE (Multipurpose Applied Physics Lattice Experiment) reactors. The construction of these reactors was completed in 2000 but they never became operational. After 8 years of attempting to overcome obstacles in design flaws, budget limitations, and safety concerns, the Atomic Energy of Canada Limited cancelled the program in May 2008. This made America's Mo-99 supply solely reliant upon the old NRU reactor, which previously was shut down multiple time . After the NRU ceases operations, the 4 other high-capacity reactors in the world are unlikely to be capable of increasing production to meet worldwide molybdenum demand long term. [3]
Through understanding the current economical standing of these medical radioisotopes as well as factors that are likely to influence their availability, future shortages may be avoided. In the Analysis of Utilization of Radioisotopes report generated in Korea, Park et al. point to major causes of the growth in both industrial and medical production of radioisotopes as being attributed to the increased presence of processed radiation sources produced at Hanaro and cyclotrons in Korea. [4] Domestically and internationally, they claim that the market size of radiation sector has been growing continuously. They expect the size of the global radiation industry and market to grow roughly 2.7 times from KRW 172 trillion (in 2011) to KRW 464 trillion (in 2020). KRW is the Korean Won, which is equivalent to 0.00089 USD meaning the projected growth will be equivalent to 153.1 billion USD to 4.13 billion USD in 2020. [4] The current supply of Mo-99 is greater than 135% of the demand. [2] As this indicates, there seems to be little reason to worry about the security of these medical radioisotopes in the future without the closure of nuclear reactors. Through keeping a close eye on the market supply and demand of these radioisotopes, future shortages are avoidable.
© Olivia Sheppard. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
[1] S. Carlson, "A Glance at the History of Nuclear Medicine," Acta Oncol. 34, 1095 (1995).
[2] "Supply of Medical Radioisotopes," U.K. Houses of Parliament Postnote Number 558, July 2017.
[3] A. J. Einstein, "Breaking America's Dependence on Imported Molybdenum," JAAC Cardiovasc. Imag. 2, 369 (2009).
[4] C. H. Park et al., "Analysis of Status of Radiation/Radioisotopes Utilization," J. Radiat. Prot. Res. 42, 1 (2017).
