Sliding gingerly into the pipe like a worm exploring its lair, the endoscopic camera found its target. In October, engineers at a nuclear reactor in Petten, in the Netherlands, pushed this instrument into a duct that carries water for the reactor’s cooling system. On their screens, they could see the problem: a bulge in the surface of the pipe. And it had grown larger since the last time they checked it. “It’s like a small part of your finger. It’s small, very small,” emphasizes Ronald Schram, a spokesman for NRG, the operator of the reactor.

Although diminutive, this deformity flung the radiopharmaceutical supply chain into disarray last month, leading to the cancellation of thousands of patient appointments. Radioisotopes—unstable forms of chemical elements that release radiation—are a vital resource in medical imaging. Despite this, only a limited number of sites produce them, meaning their supply can be squeezed.

NRG’s Petten reactor is one of just six major commercial producers of molybdenum-99, a key medical radioisotope. Molybdenum-99 decays into technetium-99m, which doctors sometimes inject into patients. It’s very safe. The technetium-99m flows into a person’s blood and collects, briefly, in parts of the body such as the heart, lungs, or a cancerous tumor. It is easily picked up by special cameras and allows doctors to take scans, which—unlike an MRI or CT scan—reveal how such parts of the body are actually functioning as well as what they look like.

While molybdenum-99 shortages occur every few years, sources who spoke to WIRED say this was a relatively acute one. Some patients in the UK faced cancellations of their hospital appointments, and some hospital tests in the Netherlands were postponed, for example. But one medical radioisotope expert says they are worried that additional shortages could occur within the coming months.

The Petten reactor produces enough molybdenum-99 to supply millions of patient doses of technetium-99m annually. October’s shutdown happened to occur at exactly the same time as one of the other six reactors that make molybdenum-99 was offline for maintenance, meaning a shortage was unavoidable. “It was unfortunate timing,” says Schram.

The slightly bulging pipe was an inescapable problem. In a nuclear reactor—not least a 60-year-old one like this—regulations insist that you can’t ignore deformities in the equipment. And so, staff shut the reactor down. There are just a handful of molybdenum-99 producers in Europe, with others in Australia and South Africa, for example.

“I remember in Geneva, two months ago, we said, ‘Pay attention, because on this specific week there is a risk of shortage if there is any problem with one of the active reactors’—and that’s what happened,” recalls David Crunelle, a spokesman for Nuclear Medicine Europe (NMEU), an industrial association.

Because of their very nature, it’s impossible to stockpile these radioactive substances—they are fleeting. Technetium-99m works as a radioactive tracer because, as it decays, it flings out gamma rays with a photon energy of 140 KeV. This is “fairly ideal” for detection using a gamma ray camera, says Cathy Cutler, chair of isotope research and production at Brookhaven National Laboratory in the US.

But technetium-99m has a very short half-life, just six hours or so. Hence why radioisotope-producing facilities send miniature generators containing molybdenum-99 out to hospitals. These generators, sometimes called “moly cows,” produce the desired technetium-99m as the molybdenum-99 decays—a bit like a portable vending machine for technetium-99m, which runs out after about two weeks, once the molybdenum-99 has completely decayed.

Glenn Flux, head of radioisotope physics at London’s Royal Marsden Hospital and Institute of Cancer Research, says the thing that makes a technetium-99m scan different to, say, a CT or MRI scan, is that it reveals how patients’ organs or a tumor are functioning—for example by revealing blood flow to the area in question.

“The CT will show you if there’s a tumor, but the technetium or other isotopes will tell you whether it’s active or aggressive,” explains Flux.

The recent radioisotope shortage caused a few thousand appointment cancellations in the UK alone, estimates Stephen Harden, vice president of clinical radiology at the Royal College of Radiologists (RCR). Health care staff swung into action to distribute the remaining radioisotope supplies around the UK, in order to ensure that the most urgent patients—those with cancer, for instance—were still able to attend their scans. “If there hadn’t been a nationally coordinated policy, there would have been significant regions in the country with no supply at all,” says Harden.

Crunelle and colleagues at NMEU continually monitor medical radioisotope production at key reactors around the world. They learn about maintenance schedules well in advance, and, as such, NMEU will often advise reactor chiefs to push these dates back slightly—for example, in order to help minimize the risk of multiple shutdowns occurring at the same time. NMEU staff use software, a kind of reactor maintenance calendar, that allows them to forecast production levels. But sometimes unpredictable events occur, such as the problem with the pipe in Petten.

“We have taken a number of technical and organizational measures in order to get started again,” says Schram, as he explains that staff at NRG were able to restart the reactor on November 4. His colleagues have not yet fixed the pipe but have, in the meantime, undertaken a safety evaluation and additional monitoring.

“There is no issue with the system,” stresses Schram. “Nuclear safety is such [that] if you see some deviation, that means you stop.” When asked whether the concern is that the affected pipe could, in the worst-case scenario, interfere in some way with the proper functioning of the reactor’s cooling system, he confirms, though adds: “You are very far away from any issue with cooling.” The plant’s engineers have scheduled a pipe repair for December.

The RCR says that, with Petten back online, deliveries of molybdenum-99 to hospitals are now returning to normal. But Flux points out that the low number of facilities that make this isotope means future shortages are likely. “I’d put money on the table that within six months we’re going to have another wobble of some sort,” he says.

Efforts to establish new producers of molybdenum-99 are afoot. NRG, for one, is currently building a completely new reactor, called PALLAS, which Schram says should become operational around 2030. At that point, NRG will stop producing medical radioisotopes at its older Petten reactor. The new PALLAS reactor will allow staff to increase radioisotope production from 260 to 300 days per year, adds Schram. In all, the new facility ought to supply significantly more doses of technetium-99m.

The recent shortage also affected health care providers in the US, according to Jeffrey Chamberlin, assistant deputy administrator for material management and minimization at the US National Nuclear Security Administration (NNSA).

“We’ve been working in the United States to stand up a domestic supply of moly-99 here,” he says. “This crisis only highlights the need for us to continue to support that.”

Currently, there is no commercial production of molybdenum-99 anywhere in the US. However, in July, the US Department of Energy and the NNSA announced a $32 million award to support the development of a molybdenum-99 production facility in Wisconsin, which is currently under construction. The structure, dubbed Chrysalis, is the work of Shine Technologies.

“We aim to end these shortages,” says Greg Piefer, founder and CEO of Shine Technologies. His company already produces another medical radioisotope, lutetium-177, but Shine Technologies needs the new building to house its molybdenum-99 equipment. Piefer’s plan is to fire an isotope of hydrogen called deuterium in a beam towards an enclosure containing highly radioactive tritium gas, tritium being another hydrogen isotope.

These hydrogen isotopes will then combine through nuclear fusion, and in that process release neutrons. As the neutrons zip away, the hope is that they will strike large uranium atoms dissolved in a liquid passing directly underneath the fusion reaction. About 6 percent of the time, these collisions will create molybdenum-99, says Piefer. The liquid target helps avoid waste, also. “We’re able to recycle that target and use it over again,” he adds.

It won’t be for another two or three years before this facility is up and running, says Piefer, but once it is, the intention is to produce 20 million doses per year. One challenge that Shine Technologies faces is that the market for molybdenum-99 is very well established, and despite its importance, this particular radioisotope does not command a high price tag. Government-subsidized reactors in other countries make it hard to compete, explains Piefer.

Other organizations are working on different means of producing molybdenum-99, including at existing nuclear reactors that are used for generating electricity, such as at Darlington Nuclear Generating Station in Ontario, Canada. “That could be a game changer,” says Cutler.

And Nick Sherman, deputy head of division for nuclear technology development and economics at the international Nuclear Energy Agency, suggests that, as new medical radioisotopes used for treating diseases become more widely available, this could, by extension, improve radioisotope supplies more generally, including of molybdenum-99.

The key takeaway from all this, though, is that health experts expect to see growing demand for medical radioisotopes as time goes on. Harden at the RCR points out that aging populations and the growing prevalence of cancer and other conditions all mean that doctors will require these diagnostic tools ever more frequently in the coming years.

“It’s really important that we plan now to try and secure those future supplies,” he says. “This is such an important area of medical imaging.”

Updated 11-27-2024 11:45 am GMT: Petten’s location was corrected from Belgium to the Netherlands.