The domestic production project for actinium-225 (Ac-225), a next-generation cancer treatment radioisotope that had been halted for more than a year due to a budget gap, will resume next year.
If a rare isotope that is produced at only one-thirtieth of global demand can be supplied stably in Korea, the shortage of raw materials needed for clinical research at research institutes and for new drug development of radiopharmaceuticals at corporations is also expected to ease.
◇ After approval, a year of standstill… first production targeted for the second half of next year
The Korea Institute of Radiological & Medical Sciences, a radiation medicine specialist agency under the Ministry of Science and ICT, received approval in May last year from the Nuclear Safety and Security Commission for cyclotron (particle accelerator)-based Ac-225 production. It came seven years after production was first reviewed in 2018. The initial goal was first production by the end of the same year.
But the project then made little progress for more than a year. About 2 billion won in the budget needed to reinforce Ac-225 production facilities and introduce equipment was pushed down the priority list during National Assembly deliberations last year and was not secured.
The budget in question was to be used to build radiation shielding and safety facilities for Ac-225 production. Ac-225 is produced by firing a proton beam at radium-226 (Ra-226). In this process, when the sealed container of Ra-226 is opened, radon gas and gamma rays are generated, so new lead shielding and harmful gas monitoring equipment must be installed.
The project regained momentum as the related budget was reflected in the first half of this year. The institute plans to begin regular production in the second half after construction and test production in the first half of next year.
If lead procurement and gas monitoring equipment purchases proceed simultaneously, the construction period is expected to be around a month. However, procurement procedures are a variable. Both lead and equipment must go through the Public Procurement Service, which takes longer than direct transactions.
Lee Gyo-cheol, Director General of the RI Applications Department at the Korea Institute of Radiological & Medical Sciences, said, "If all processes run in parallel, we could finish within the first quarter."
After construction, a facility modification permit must be obtained again from the Korea Institute of Nuclear Safety (KINS). Lee said, "The time required for approval is also a variable," and predicted, "Once approval is granted, test production will be possible in the second quarter and regular production in the second half."
In theory, the production scale per run is expected to be 1–2 mCi, enough to treat three to four patients. Once regular production begins, the institute plans to establish a system to produce twice a month.
The institute is also developing solid-target technology that can increase output by 10–15 times. Currently, radium is dissolved in liquid and irradiated with a beam, resulting in low conversion efficiency.
Lee, the Director General, said, "If we manufacture a solid-target device in 2028 using a patent the institute already holds, we expect to ramp up production around 2029," adding, "We also have commercial supply in mind, but no specific approach has been decided yet."
◇ The world in an "Ac-225 scramble"… breathing room for domestic clinical trials and new drug development
Ac-225 is a radioisotope that emits alpha particles. It is used as a key raw material for targeted radionuclide therapy (TRT), which delivers radiation only to cancer cells, and is drawing attention as a next-generation isotope in the treatment of hard-to-treat cancers such as prostate cancer and neuroendocrine tumors.
Supply is the problem. Annual global demand reaches about 1,850 GBq, but actual production is only 67 GBq as of 2024. That is about one-thirtieth of demand.
As the produced volumes are prioritized for countries with active clinical trials such as the United States and Europe, domestic research institutes and corporations have repeatedly failed to secure raw materials when needed.
The institute is currently conducting joint research on Ac-225-based radiopharmaceuticals with SK Biopharmaceuticals(326030), FutureChem(220100), and others, and corporations are importing most of the raw materials needed for the research from countries such as the United States and Germany.
Lee, the Director General, said, "Once domestic production begins, the import expense burden will fall and research timelines can be managed much more stably," adding, "At present, when overseas supply is cut off, joint research schedules are often pushed back together."
Lee added, "If raw material procurement conditions improve, the entry barriers to research and development of Ac-225-based radiopharmaceuticals will also come down."
As supply shortages worsen, global corporations are also entering the race to secure production capacity. TerraPower, a U.S. nuclear corporation founded by Bill Gates, announced in March plans to invest about $674 million (about 960 billion won) to build an Ac-225 production facility in Philadelphia.
When domestic production begins, patient access to treatment is also expected to improve. In Korea, outside of a few clinical trials, there is virtually no way to receive Ac-225-based therapy.
Lee, the Director General, said, "Domestic demand for Ac-225 therapy has not yet been sufficiently assessed, so it is difficult to present a specific annual supply scale," adding, "However, because there are currently not many medical institutions administering Ac-225 therapy, we expect to be able to fully meet domestic demand in the initial production phase."
Lee added, "Once production stabilizes, we plan to gradually increase the number of production runs to reflect demand."