More than 80% of the medical imaging used each year to diagnose diseases like cancer is made possible by the pharmaceutical drugs produced, for the most part, in research reactors. These radiopharmaceuticals contain the radioisotope technetium-99m (99mTc ), which comes from the radioisotope molybdenum-99 (99Mo) that is primarily produced in research reactors.
"While 99Mo or even 99mTc can be produced using other approaches, research reactors are particularly cost-effective and well-suited to this, especially for commercial, large-scale production," said Joao Osso, Head of the IAEA's Radioisotope Products and Radiation Technology Section. "This is because they can produce large amounts of 99Mo with the right characteristics that make it easy to extract 99mTc using a generator in a hospital, thereby keeping supplies of radiopharmaceuticals flowing consistently and reliably for more patients."
From reactor to patients
Research reactors are reactors that, instead of generating electricity, are primarily used to produce neutrons for other applications. These neutrons can be used for various purposes, such as to produce 99Mo by irradiating uranium-235 targets.
Being a radioisotope, 99Mo is an unstable atom that undergoes decay. It takes 66 hours for half of any 99Mo produced to decay - this is known as its half-life. The decay product of 99Mo, also called its 'daughter product', is 99mTc.
To get 99mTc, the irradiated uranium-235 targets are moved to a processing installation, usually near a research reactor, to separate 99Mo from the other fission products and purify it. The purified 99Mo is then transported to a production facility for 99Mo/99mTc generators - devices used to safely hold, transport and chemically extract 99mTc from 99Mo directly on site at a hospital or other medical facility.
Inside a typical generator, aluminium oxide containing 99Mo is washed with a saline solution. The 99Mo clings to the oxide, whereas the 99mTc is removed by the solution. This produces a 99mTc solution that is then used to create different radiopharmaceuticals ready to be injected into a patient's body. Once inside the body, the small amounts of radiation released by the decaying 99mTc are detected by a special camera outside the patient's body to create medical images for diagnosing diseases.
Molybdenum-99 target plate and the holder used to irradiate the plates in a research reactor. (Photo: Necsa)
Short half-lives, constant production
As 99mTc has a half-life of six hours, it must be used quickly after it is extracted otherwise it loses its effectiveness. With 99Mo's short lifespan and 99mTc's being even shorter, they have to be constantly produced to meet global demand.
One of the major global producers of 99Mo, and of other radioisotopes, is the South Africa Fundamental Atomic Research Installation (SAFARI-1), which is part of the South African Nuclear Energy Corporation (Necsa) and is the leading medical isotope-producing research reactor on the African continent. In collaboration with the radioisotope supplier, NTP Radioisotopes SOC Ltd - a subsidiary of Necsa - the SAFARI-1 reactor has become one of the world's 5 largest suppliers of 99Mo and is part of the medical radioisotope supply chain for more than 50 countries worldwide. It now produces around 20% of the global 99Mo demand, and the 99mTc derived from generators using SAFARI-1's 99Mo is used in more than 40 hospitals and other health facilities across Africa.
"Becoming a global player in the radiochemical and radiopharmaceutical community has been a matter of implementing management systems, maintenance programmes, personnel training and strategic plans in a well-structured and controlled way," said Koos du Bruyn, Senior Manager at SAFARI-1. This has also supported the reactor's secondary use for research and education and for industry.
With the IAEA's support, SAFARI-1 has undergone continuous development and improvements since it began operation in 1965, including its conversion from high enriched uranium fuel to low enriched uranium fuel in 2009 (learn more about this kind of conversion) and its transition from high enriched to low enriched uranium targets, which was completed in 2017. These activities have helped to ensure better utilization of the reactor and its successful transition to more commercial use.
"In the 1990s, we changed our operational approach and put more emphasis on maintenance and management, including building up a team of specialized staff who are highly skilled in a range of areas. This allowed us to go from being a low-use reactor to an extremely high-use and more sustainable facility," du Bruyn said. In the nine years between 1995 and 2004, the reactor was used more than in the previous three decades combined. Then only seven years later it achieved the same result. As of 2019, SAFARI-1's use has almost quadrupled since 1995.
In the last 15 years, SAFARI-1 has operated around the clock, nearly non-stop for around 300 days each year and is expected to continue supplying 99Mo until at least 2030. However, as the reactor is ageing, a new 15 to 30 MW (thermal) multipurpose research reactor (MPR) is being considered to replace it. This process will take up to ten years from the start of feasibility studies to completion.
"If a new MPR is built, it will be equipped to flexibly operate over the next 60 or more years so we can adapt to potential changes, such as fluctuations in medical isotope markets and research requirements, as well as provide South Africa and the region with a critical nuclear fuel and material testing facility," du Bruyn said.
This article was also featured in the IAEA Bulletin on Research Reactors published in November 2019.