New isotope initiatives address supply challenges

The US Department of Energy's National Nuclear Security Administration (NNSA) award of USD35 million to Wisconsin-based SHINE Technologies will support the commercial production of Mo-99 to help establish a reliable supply of the isotope, the agency said. This is the third of four agreements since the NNSA in July 2020 announced it would make funds available to industry to start domestic commercial-scale production of Mo-99 - previously sourced from overseas - by the end of 2023. It follows two cooperative agreements worth a total of USD37 million to NorthStar Medical Technologies, LLC, which were announced in August. Negotiations for a fourth award are ongoing, NNSA said.

Mo-99 is used in more than 40,000 medical procedures in the USA each day, including the diagnosis of heart disease and cancer. In 2012, the US Congress directed NNSA to establish a programme to support the development of commercial domestic production of Mo-99 without the use of highly enriched uranium, which is seen as a proliferation risk. The NNSA's Mo-99 Program is implement through the Office of Defense Nuclear Nonproliferation.

"This cooperative agreement is a triple win for the United States," DOE Under Secretary for Nuclear Security and NNSA Administrator Jill Hruby said. "NNSA's continued partnership with SHINE will help ensure that doctors and patients get the medical isotopes they need, that those isotopes are produced without the use of proliferation-sensitive HEU, and that the work gets done here in the United States."

New route to Ac-225

Ac-225 is an extremely rare alpha-emitting radioisotope that can be used in targeted alpha therapy (TAT), a new type of therapy in which an alpha particle emitter is combined with a substance such as a monoclonal antibody to carry the alpha emitter to the target cells. This enables highly precise treatment of tumours with minimal impact to surrounding healthy tissue. Pre-clinical studies have shown TAT to be extremely effective against some forms of cancer that are difficult to treat with existing methods.

Japanese company Hitachi Ltd, Tohoku University and Kyoto University yesterday announced their development of a linear accelerator-based method of producing Ac-225 that does not involve nuclear material. The method, which involves using a highly penetrating type of radiation known as bremsstrahlung radiation to irradiate radon-226, has been developed by Hitachi, Tohoku University's Research Center for Electron-Photon Science, and Kyoto University’s Institute for Integrated Radiation and Nuclear Science by applying Hitachi's accumulated experience and technologies from the fields of particle therapy and nuclear power generation, they said.

As well as being an efficient method of producing Ac-225, the technique does not produce difficult-to-separate impurities, making a high-quality product.

The team has conducted a proof-of-principle test on the production of Ac-225 using Ra-226 and used findings from the test to successfully produce about 370 kBq of the isotope, an amount the researchers say is sufficient for the future evaluation of its applicability in pharmaceutical products. This is a "major step forward" for commercial application of this production method, they said, estimating that the technique would enable the equivalent of one year's current production of Ac-225 - around 63 GBq - could be produced in one day.

Some of these results will be shared at the 34th Annual Congress of the European Association of Nuclear Medicine, taking place later this month, Hitachi said.

Canadian-German partnership

Separately, German radiopharmaceutical biotech company ITM Isotope Technologies Munich SE and nuclear science and technology organisation Canadian Nuclear Laboratories (CNL) have signed a Memorandum of Understanding to explore the development and industrial-scale production of Ac-225. The MoU will see the two organisations collaborate on the development, manufacturing, and distribution pathways for the medical radioisotope.

One of the biggest challenges in harnessing the full potential of the alpha-emitter is ensuring its supply, the two organisations said, adding that together they have the expertise and infrastructure to sufficiently bypass the supply hurdle.

CNL President and CEO Joe McBrearty said the agreement will make use of CNL's capabilities in target development, radiochemistry, radioisotope analysis and by-product management. "Working with ITM, we hope to leverage these capabilities to accelerate the development of this promising new isotope, and to establish a commercial pipeline for what we believe will be a ground-breaking new cancer treatment," he said.

ITM CEO Steffen Schuster said the company looked forward to sharing its expertise in the global production and supply radioisotopes in a shared mission of exploring the "otherwise untapped potential" of Ac-225, commonly referred to as the 'rarest drug on earth'. "We are eager to unveil the therapeutic value of this radioisotope which we believe has the potential to unlock revolutionary TAT treatments," he said.