U.S. moves closer to establishing domestic supply of Mo-99 for nuclear imaging

The majority of these imaging scans are for oncology and cardiology. In oncology Mo-99 derived isotopes are used to determine the extent of disease, cancer staging, managing treatment options and assessing the impact of those treatments. In cardiology, the isotopes are used to determine if a patient needs to undergo surgical or interventional revascularization. So, the stakes are high.

A global reliance on aging isotope reactors

Historically, Mo-99 has been sourced from a handful of older research reactors outside the U.S., much of which came from the Chalk River reactor in Canada. But that 60-year-old reactor closed in 2018, and the reliance on reactors outside the states, including one Russian reactor for some medical isotopes, has left the U.S. vulnerable to supply chain disruptions.

“The world depends on six reactors, many of which are decades old,” Cutler explained. “These facilities coordinate their operations to minimize disruptions, but when maintenance issues arise, shortages can quickly follow.”

Unfortunately, she said radioisotopes are not something that can just be manufactured and stockpiled for when they are needed, as they need to be made constantly because of their short shelf-life.

"Technium-99m has a six hour half-life. So, an analogy is trying to make ice and keeping it from melting while shipping it around the country. It's only going to last for so long. And that's what the challenge is with isotopes. They have very short half-life, so we're making them as patients need them. We can't put it on a shelf like Ibuprofen and pull it out when we need it," Cutler said.

Efforts to bring Mo-99 production to the U.S.

In recent years since the Chalk River closure, Cutler the DOE and NNSA have invested heavily in fostering a domestic Mo-99 supply. Despite initial successes, including Wisconsin-based NorthStar Medical Radioisotopes' entry into the market, economic challenges have hindered progress. NorthStar ceased production using its U.S.-based reactor supply line in October 2023, citing an inability to compete with subsidized international reactors. Medicare created an add-on payment to help incentivize purchase of domestically made Mo-99 products, but it was not enough.

When NorthStar said it U.S. Mo-99 production was not profitable, investors lost interest in a couple of other companies that had accepted tens of millions in federal grants and now appear defunct, or they abandoned pursuit of Mo-99 production.

However, Cutler said a promising development remains on the horizon. Shine Technologies, another Wisconsin-based company exploring non-reactor-based production methods, recently secured $32 million in federal funding to advance its Mo-99 production capabilities.

Additionally, the University of Missouri is planning to build a second research reactor to support isotope production, though it is expected to take 8 to 12 years to become operational.

“In five to 10 years, I believe we will see significant progress,” Cutler said. “But this requires ongoing support from Congress to ensure we meet the growing demand for nuclear imaging and therapeutic isotopes.”

Mitigating nuclear proliferation risks is a key reason U.S. government supports domestic production

Beyond economic viability, national security concerns have driven efforts to reduce reliance on foreign sources. Historically, Mo-99 production involved highly enriched uranium (HEU) which was produced in the U.S. and sent to reactors overseas, raising nuclear weapon proliferation risks if these shipments were intercepted. In recent years, international cooperation facilitated a switch to low-enriched uranium (LEU) targets, with the final transition completed by 2022, Cutler explained.

The NNSA grant program to jump-start domestic Mo-99 production aimed at helping U.S. companies that could innovate and come up with solutions that did not use HEU.

Read more in the recent article Why is the U.S. still dependent on foreign medical isotope production?