Supply of Medical Radioisotopes

DOI: https://doi.org/10.58248/PN558 

Summary of Key Points

• Radioactive isotopes are essential tools in medicine for both diagnosis and treatment, but rapid radioactive decay means that they cannot be stockpiled. They are made in ageing nuclear research reactors outside the UK.
• Following previous radioisotope shortages, the NHS has reduced the amount of radioisotopes used through efficiency savings.
• Long-term security of supply may rely on investment and agreements with international producers, or investing in new technology to produce them in the UK.
• The Government has stated that withdrawal from the European Atomic Energy Community (EURATOM) will not affect the UK’s ability to import medical radioisotopes.
• Therapeutic use of radioisotopes is a small field, but expected to grow rapidly in the next decade, as new drugs are developed.

Contributors & Reviewers

• The Board of the Parliamentary Office of Science and Technology
• Dr Jim Ballinger – King’s College London
• Kevin Charlton – OECD Nuclear Energy Agency
• Professor David Cope – Clare Hall, University of Cambridge
• Jilly Croasdale – Head of UK Radiopharmacy Group, Sandwell and West Birmingham Hospitals NHS Trust
• Dr Kevin Crowley – Nuclear and Radiation Studies Board, The National Academies of Sciences, Engineering, and Medicine
• Roy Brown – Curium
• Professor Erika Denton – Associate Medical Director Honorary Professor of Radiology Norfolk & Norwich University Hospital
• Dr Glenn Flux – Royal Marsden NHS Trust
• Dr John Dickson – Institute of Nuclear Medicine, University College London Hospital
• Aurelie Gasse – GE Healthcare
• Dr Adrian Hall – The Royal Marsden NHS Foundation Trust
• Dr Neil Hartman – Head of Radiopharmacy and Nuclear Medicine, Barts Health NHS Trust
  
• Dr James Harvey – NorthStar Medical Technologies
• Dr Ondrej Lebeda – Nuclear Physics Institute, Academy of Sciences of the Czech Republic
• Professor Bill Lee -Imperial College London
• Howard Marsh – Alliance Medical
• Dr Hywel Owen – University of Manchester
• Dr John Rees – Department of Radiology, University Hospital of Wales
• Lars Roobol – Dutch National Institute for Public Health and the Environment
• Dr Jane Sosabowski, Queen Mary University of London
• Dr William H Thomson – Head of Physics and Nuclear Medicine, City Hospital Birmingham
• Titus Tielens – PALLAS
• Dr Richard Zimmerman – Chrysalium Consulting SARL
• Civil Nuclear & Resilience Directorate, Department of Business, Energy & Industrial Strategy
• Medicines and Pharmacy Directorate, Department of Health

Background

Radioisotopes are essential tools used in medicine and research. They are made outside the UK in ageing nuclear research reactors that are subject to planned and unexpected shutdowns, which increases the risk of shortages of isotopes. This POSTnote explores how these isotopes are made, what they are used for, and the challenges for the UK in ensuring the continuity of their supply in the short, medium and long-term, and the implications of the UK’s exit from the EU.

What are Radioisotopes?

Radioisotopes are unstable chemical elements that undergo radioactive decay. During decay they change form and emit excess energy as radiation.

What are they used for?

They are essential tools used in nuclear medicine, where they are typically combined with a drug that guides the radioisotope to a particular part of the body. These drugs are prepared in radiopharmacies; the UK is served by a network of more than 100 radiopharmacies, many of which are part of hospitals’ nuclear medicine departments.

Depending on the radioisotope and the procedure, the radiation is either detected by a scanner to produce an image (diagnosis), or damages target cells in the body (therapy). In the UK, around 700,000 nuclear medicine procedures using radioisotopes are carried out each year, such as diagnosing coronary disease, detecting the spread of cancer to bones, and treating thyroid cancer. Radioisotopes are also an important tool for biomedical research.

Isotopes with therapeutic uses, such as iodine-131, can also be made in research reactors and their supply is of potential concern. Radiotherapeutics is a small field, accounting for fewer than 5,000 procedures in the UK in 2015. Iodine-131 is used to treat thyroid cancer and radium-223 is used to treat bone metastases arising from prostrate cancer. Recently the field has been growing, driven by an interest in radioisotopes known as alpha and beta emitters.

How are Radioisotopes Made?

⁹⁹Mo The most commonly used radioisotope is technetium-99m (^99mTc), accounting for over 80% of diagnostic medicine procedures. ^99mTc is produced by the radioactive decay of molybdenum-99 (⁹⁹Mo), made in nuclear research reactors through the fission (splitting) of enriched uranium. Neither isotope can be stockpiled because they decay rapidly: the amount of useful radiation emitted by ^99mTc halves every 6 hours, and the yield of ^99mTc obtained from ⁹⁹Mo halves every 66 hours.

Where are they made?

This table lists reactors that produce more than 90% of the world’s ⁹⁹Mo supply and cites their maximum production capacity.

**NRU is on standby until March 2018, when it will close permanently.*Global demand as estimated by the OECD-NEA and includes a 35% buffer for outage reserve capacity.⁴ Total production capacity adds up to more than 100% of global demand because reactors mostly operate at below their maximum capacity.

Alternative technologies for producing ^99mTc have been investigated since a radioisotope shortage in 2009. None of these are in routine use, but some are likely to enter the market within the next few years. One mature technology is using cyclotrons: particle acclerators used in medicine, industry and research. Cyclotron-produced ^99mTc is being evaluated in clinical trials to assess whether it can replace reactor-derived material.

Some cyclotrons can directly produce ^99mTc (rather than its precursor ⁹⁹Mo) by bombarding ¹⁰⁰Mo with protons (positively charged particles). Advantages of this process are that it does not depend on uranium as a source material and that it produces less radioactive waste. Work to develop this process is being led by Canadian teams at the national laboratory for particle physics (TRIUMF) and the University of Alberta.

Other processes using reactors and accelerators are also in development. The US Department of Energy National Nuclear Security Administration (DOE NNSA) has funded five companies to develop domestic ⁹⁹Mo production, alongside several private initiatives. It is not certain that all of the technologies used by these companies will work on a commercial scale, or produce ⁹⁹Mo at a competitive price.The most mature projects are:

• NorthStar plans to produce ⁹⁹Mo with two different projects: one uses a research reactor but replaces the uranium source material with ⁹⁸Mo, and plans to begin production in 2018. The other uses a particle accelerator to bombard a ¹⁰⁰Mo target with photons, and plans to start production in 2020. It estimates that both projects could supply 49% of global demand by 2022.
• SHINE plans to produce ⁹⁹Mo by bombarding uranium salts with neutrons from an accelerator. It aims to begin production in 2020 and hope to meet 32% of global demand by 2022.
• General Atomic and Nordion plan to produce ⁹⁹Mo in a research reactor with new extraction technology. It plans to begin in 2019 and expect to produce 26% of global demand by 2022.

Issues in the Supply Chain

• Production in nuclear research reactors: most research reactors that produce ⁹⁹Mo were built in the 1950s and 1960s and are approaching the end of their lifespans, increasing the length of shutdowns for routine maintenance and the likelihood of unplanned outages. Investment in new facilities has been limited.
• Transport of radioactive materials into the UK: Transport delays reduce the amount of useful radioactive product left. In 2008 the closure of the channel tunnel after a fire led to a short-term shortage of ⁹⁹Mo, and industrial action in Calais in 2015 also delayed deliveries.
• Nuclear non-proliferation: reactors produce ⁹⁹Mo from highly-enriched uranium (HEU) or low-enriched uranium (LEU). Production using LEU is less efficient and more expensive but HEU is a proliferation risk and all major producers of medical radioisotopes have agreed to convert to using LEU. Five of the six operational reactors use at least some HEU, although they are in the process of converting to LEU.

Future demand and supply

Global ⁹⁹Mo demand is estimated by the Organisation for Economic Co-operation and Development’s Nuclear Energy Agency (OECD-NEA). It forecasts growth in demand to be 0.5% per year in developed countries, which account for 84% of global demand, and 5% in developing markets leading to an overall growth of 1.2% per year.

• Short term supply (1-2 years) – has been affected by the closure of the reactor in Canada. The NEA, the Association of Imaging Producers and Equipment Suppliers and several companies consider supply will be reliable in the short term.⁴
• Medium term supply (until 2022) – the NEA predicts that existing reactors can meet forecast demand. Organisations involved in establishing new reactors and technologies expect to bolster supply, though some of the new methods may not succeed. 
• Long term supply (beyond 2021)- a number of factors discussed in detail in the paper make it difficult to predict security of supply in the long-term (beyond 2021).

Securing Future Supply

Increased security of supply in the UK could be achieved through reducing ^99mTc use, relying on accelerator production, investing in new reactors overseas, supporting the market and mitigating any potential effects of Brexit.

Designing clinical services to reduce ^99mTc use

Since 2009, radiopharmacies have reduced the amount of ^99mTc they need through efficiency savings. Many radiopharmacies have achieved this by optimising generator management, delivery and extraction schedules, sometimes assisted by specialised software. Some nuclear medicine departments have gamma cameras that use special software which can produce comparable quality diagnostic images using a lower (as much as 50%) dose of the radioisotope. In the absence of any systematic review of radiopharmacies’ actions to reduce ^99mTc use, it is not known if these efficiency savings have been widely adopted across the NHS.

The Administration of Radioactive Services Advisory Committee notes that weekend working could enable more efficient use of generators. Nuclear medicine departments do not routinely operate over weekends but some did during shortages. The British Nuclear Medicine Society (BNMS) argues that 7-day working would put pressure on an already stretched workforce and would need to be fully funded to be effective. Its 2014 report concludes that “patients will be poorly served by not having a cheap, plentiful supply of ^99mTc”.

Implications of Brexit on the Availability of Radioisotopes

The European Atomic Energy Community (Euratom) regulates civilian nuclear activity and supports the “secure and safe supply and use of medical radioisotopes”. The Government confirmed the UK’s withdrawal from Euratom in an explanatory note to the EU (Notification of Withdrawal) Bill. It considers that the Euratom and EU Treaties are legally joined such that triggering Article 50 gave notice of leaving Euratom. There is a debate about the legal basis of this point. This is also the European Commission’s position: a recent statement said that the Euratom Treaty will cease to apply to the UK on 30 March 2019. The Government will establish new agreements to replace Euratom before March 2019. Concerns have been raised by stakeholders across academia and industry as to how realistic this is, and its potential negative impacts on the UK’s nuclear sector, including nuclear research, power and medicine. Although there has been speculation that the UK will be unable to import radioactive materials, including ⁹⁹Mo the Government has recently stated in a parliamentary question on 27 June that Euratom does not apply to the import and export of medical radioisotopes, as they are not fissile materials.