The industry’s ability to generate a return on billions of dollars of investment rests on a heavily regulated supply chain defined by time-pressured logistics.
Some of the world’s biggest drugmakers have invested heavily in radiopharmaceuticals in recent years, striking multi-billion dollar deals to secure assets with the potential to transform cancer treatment. Frontrunner Novartis recently opened a 10,000-square-foot facility as part of a $23 billion investment in U.S. infrastructure. Yet the rapid emergence of the sector has strained the infrastructure needed to support the modality, whose unique needs range from the reactors that generate isotopes to the facilities that treat patients.
Companies have encountered challenges as the radiotherapy sector has emerged. RayzeBio paused enrollment in a Phase III trial of RYZ101 last year due to a shortage of the radioisotope actinium-225. Novartis faced quality issues and shortages as it scaled up production of Lutathera and Pluvicto to meet rising demand. The setbacks point to the central role of the supply chain in access to these therapies.
“The lack of access to these drugs, for a lot of folks, was not necessarily due to a limitation of science, but due to a limitation of the logistics and manufacturing and engineering needed to get these drugs out to the world at a cost of scale that matters,” Justin Butler, a partner at Eclipse Ventures, told BioSpace.
For lutetium-177, the isotope used in Lutathera and Pluvicto, the problem is simple, said Uriah Orland, director of communications at the University of Missouri Research Reactor (MURR), the sole U.S. producer of the isotope. “The demand is much higher than the supply right now.”
The Rise of Radiopharma
Radioligand therapies (RLTs) treat cancer by delivering radioactive isotopes to tumor cells. Novartis made early moves into the space in 2017 and 2018, paying a combined $6 billion to buy Advanced Accelerator Applications and Endocyte in the span of 12 months.
The clinical and commercial success of Novartis’ Lutathera and Pluvicto, which generated $2 billion between them over the first nine months of 2025, showed the promise of the modality. AstraZeneca, Bristol Myers Squibb and Eli Lilly each joined Novartis in the sector by paying between $1.4 billion and $4.1 billion to acquire radiopharmaceutical specialists in 2023 and 2024.
RLT development has increased as these and other leading drugmakers have entered the sector. Sponsors posted 12 trials involving actinium-225, a radioactive isotope, to the ClinicalTrials.gov registry between 2008 and 2021. From 2022 to 2024, 12 more were added. Then this year, activity exploded, as sponsors including AstraZeneca, Bayer, Novartis and BMS’ RayzeBio posted 13 trials in the first nine months of 2025.
Companies need access to specialized manufacturing and supply capabilities to get such treatments to patients. Butler worked with Mayo Clinic on how to meet that need, leading the investor to conclude that there is no one technological solution for RLT supply.
He compares RLT manufacture and delivery to rocket science. “Any good rocket scientist will tell you that there’s not any one part of rocket science that’s that hard. It’s making the entire thing work all together and not blow up,” Butler explained. “That’s a lot like the radiopharmaceutical space. There’s no one thing.”
Orchestrating Supply
The exact capabilities needed to make RLTs and ship them to patients vary from isotope to isotope, but the overarching challenges facing each product are similar. Production begins with isotope generation. Actinium-225 sources include thorium-229 decay and accelerator beam facilities. Lutetium-177, the active ingredient in Lutathera and Pluvicto, is made in a nuclear research reactor.
Once generated, the isotopes start to decay. Isotope half-lives vary—actinium-225’s is 9.92 days versus 6.65 days for lutetium-177—but all impose a short deadline for getting the drug to patients. Frank Scholz, CEO of NorthStar Medical Radioisotopes, told BioSpace that people outside the sector underestimate the complexity created by half-lives.
The ticking clock means materials cannot be stored without losing value. Shipping delays can result in no drug being available to treat a patient on the scheduled day. Systems such as the enterprise resource planning platforms that companies use to manage business processes must reflect the fact that the material is decaying by the hour.
At the final step of the supply chain, healthcare facilities need specialized infrastructure and staff training to handle the products and deal with the resulting radioactive waste. Most cancer patients are treated in community oncology clinics that may lack such capabilities. Some patients will travel to large academic medical centers for treatment, but others will remain cut off from RLTs until more sites add capabilities.
Activities to make and supply the therapies are covered by regulations that go beyond the FDA rules that apply to all medicines. The Nuclear Regulatory Commission oversees the reactors used to make isotopes, and the Department of Transportation regulates shipments in transit. Scholz said the level of regulatory scrutiny is another thing about RLTs that people outside the space often don’t fully appreciate.
Companies will need to understand and manage such issues for RLTs to become a cornerstone of cancer care. And tests of the robustness of the supply chain are on the horizon. With Phase III data on assets including RYZ101 expected next year, the sector is closing in on clinical evidence that could drive increased commercial use of a growing range of RLTs.
