Research reactors for medical isotopes (Mo-99, Lu-177, I-131)
Most of the world's therapeutic and scanning isotopes are made by putting targets into about half a dozen ageing research reactors and flying the product out within days. When two reactors were down at once in 2009 and 2010, hospitals worldwide ran short of the most used scan isotope.
Overview
Neutron-rich isotopes come from reactors. Molybdenum-99, parent of technetium-99m for most bone and SPECT scans, is made by fissioning uranium targets; lutetium-177 for radioligand therapy is made either directly by irradiating enriched lutetium-176 (carrier-added, with a long-lived Lu-177m impurity that complicates waste) or indirectly by irradiating enriched ytterbium-176 and chemically separating the lutetium that grows in (non-carrier-added, the route used by ITM, SHINE, Isotopia and others); iodine-131 comes from tellurium targets or fission. The irradiations happen in a small fleet of high-flux research reactors: BR2 at SCK CEN in Mol (Belgium), the High Flux Reactor at Petten (Netherlands), MARIA (Poland), LVR-15 (Czech Republic), SAFARI-1 at Pelindaba (South Africa), OPAL at Lucas Heights (Australia), MURR in Missouri and reactors in Russia. Processors such as Curium, IRE, NTP and ANSTO dissolve the targets in hot cells and ship purified product to generator and radiopharmaceutical makers; lutetium producers such as ITM, Isotopia, Eckert & Ziegler and Curium buy irradiation time and do the separation. Bruce Power in Ontario has shown that a commercial power reactor can irradiate ytterbium targets for ITM, opening a new class of supplier.
The fleet is old and outages coincide. When Canada's NRU reactor shut unexpectedly in 2009 and Petten's HFR followed in 2010, the world lost most of its Mo-99 for months; the OECD Nuclear Energy Agency's high-level group on medical radioisotopes was formed in response, pressed for full-cost pricing, scheduled reserve capacity and conversion of targets from highly enriched to low-enriched uranium (SAFARI-1 converted first), and still tracks the supply. NRU stopped isotope production in 2016 and closed in 2018; the Pallas reactor being built at Petten is the planned replacement for the HFR. Newer constraints are enriched ytterbium-176, most of which has historically come from Russian enrichment, and the surge in lutetium demand since lutetium-177 vipivotide tetraxetan was approved, which produced dose delays in 2022 and 2023.
How it works
Neutron capture or fission in high-flux research reactors, followed by hot-cell chemistry and same-week logistics for isotopes with half-lives of days.
- Large activities per irradiation
- Well characterised routes with pharmacopoeial monographs
- Power reactors can now add capacity
- Half a dozen ageing reactors with coinciding outages
- Enriched target material from few sources
- Transport of short-lived product across borders
Dependencies
Open the dependency map →Nothing recorded yet: a foundation, or a gap to fill.
Dependencies are what this technology cannot be delivered without: manufacturing steps, instruments, software, upstream methods. See its full chain on the map.
Latest papers
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