Molecular Imaging News: From Outsourced to Insourced
By Will Ascenzo
Radiology Today
Vol. 20 No. 11 P. 30

New sources of Mo-99 will soon be available in the United States.

Molybdenum-99 (Mo-99) is one of the most important radioisotopes in the modern world. Every day, in health care facilities around the world, hundreds of thousands of lifesaving medical procedures are performed that rely on radioactive isotopes developed from Mo-99, including technetium-99m and fluorine-18. The problem with Mo-99, though, is that not enough of it is being made. In fact, supply chain issues in the past, particularly in 2009 and 2016, have had devastating effects on patients all over the world, especially in the United States.

A Few Days in the Half-Life
Every radioactive isotope has a half-life, the amount of time it takes for roughly one-half of the isotope’s mass to decay into a different and less useful substance. The materials used as fuel for nuclear reactors have very long half-lives, such as uranium-235’s 700-million-year half-life. But some lab-created radioactive isotopes, such as hydrogen-7, decay in fractions of a second. On the middle of the scale are the isotopes used in medical imaging, which typically have half-lives ranging from days to hours. Only isotopes that decay at a reasonably rapid rate can be used as medical isotopes because those with longer half-lives would linger too long in the body and cause harm to the patient.

Mo-99 has a half-life of 66 hours. The isotopes that are developed from Mo-99 have even shorter half-lives. Technetium-99m, which is used for PET scans, decays by half every two hours. While isotopes with a short half-life can present challenges in getting them to patients, they are advantageous once injected because they deteriorate and leave the body quickly.

Since isotopes with a short half-life are highly volatile, there’s no way to stockpile them. New supplies of Mo-99 must be produced constantly to meet ever-growing worldwide demand for the medical procedures that rely on it.

How It’s Made
For decades, the most common way to produce Mo-99 was to use a nuclear research reactor. When uranium undergoes nuclear fission, the uranium atoms break apart into new elements and isotopes, including small amounts of Mo-99. The Mo-99 can then be isolated from the isotope soup and sent abroad to medical facilities, at which point it is used to produce the more short-lived isotopes used in medical radiography.

There aren’t many nuclear research reactors in the world that are producing Mo-99. In fact, the only reactor in North America that was producing this isotope stopped production in 2016. Currently, only a handful of reactor facilities supply the world’s stock of Mo-99. Much of the Mo-99 produced in these reactors decays while in transit across the world, and there’s nothing that can be done about it.

In addition, reactor facilities around the world are aging. In the United States, almost no new reactors are being constructed, while facilities that have been in operation for six decades or more elsewhere in the world crawl ever closer to their decommissioning. If another medical isotope-producing reactor were to shut down, temporarily or otherwise, or yields from one of these reactors were to fall below anticipated levels, another shortage would likely follow.

New Solutions
Nations around the world, especially the United States, recognize the crucial need to secure new production sources for Mo-99. New production methods that do not involve fission reactors or highly enriched uranium (HEU) targets are particular areas of emphasis. The use of HEU for Mo-99 production is seen by many in the international community as a nuclear proliferation risk, as HEU is weapons grade and can be dangerous if allowed to fall into the wrong hands.

With funding from the Department of Energy and approval from the Nuclear Regulatory Commission, four tech companies in the United States—SHINE Medical Technologies, NorthStar Medical Radioisotopes, Niowave, and Northwest Medical Isotopes—are developing new technologies and procedures for producing Mo-99 without the use of a nuclear fission reactor or HEU, potentially alleviating or preventing future shortages.

These new high-tech systems are more environmentally sound, take up much less space, can be more easily maintained, and require less regulatory oversight for safety and security, easing many supply issues associated with reactor-sourced Mo-99 production. These new solutions could soon supply enough Mo-99 to meet the majority of the world’s need and make painful shortages and supply chain issues a thing of the past. The isotopes will come from two sources:

Mo-99 From Natural Molybdenum
In the method of Mo-99 production spearheaded by NorthStar, other molybdenum isotopes are obtained from molybdenite, a naturally occurring metal. Unlike Mo-99, Mo-98 and Mo-100—which differ only in the number of neutrons they have in their nuclei—are nonradioactive and do not decay, making them stable.

New isotopes are created by adding or subtracting neutrons from existing elements. Bombarding samples of Mo-98 with neutrons causes the Mo-98 atoms to absorb a neutron and become Mo-99, or electron accelerators can “knock off” a neutron from Mo-100 atoms to convert them to Mo-99. The main benefit of these methods is that no uranium is used in the production process.

Mo-99 From Low-Enriched Uranium
Low-enriched uranium (LEU) is uranium that contains a much smaller proportion of fissile uranium-235 than HEU, making it much safer to use. Unlike HEU, LEU is not weapons grade, and considerable resources would have to be expended to render a sample of LEU into a credible threat, should it fall into the wrong hands.

Some plans for using LEU to produce Mo-99 still involve the use of a fission reactor, but, by redesigning the uranium target that produces the isotopes, comparatively large amounts of Mo-99 can be produced in a small, low-output reactor. This is the method used by Northwest Medical Isotopes. Niowave’s approach to isotope production, though similar, eschews the need for a fission reactor and instead uses an electron accelerator to split uranium atoms and create new isotopes.

Another accelerator-based method relies on nuclear fusion between deuterium and tritium to produce neutrons. SHINE Medical Technologies will use a system that includes powerful fusion-based neutron generators developed by nuclear technology company Phoenix, LLC, to produce large quantities of Mo-99 from LEU. SHINE’s isotope production facility, which is under construction, will be capable of supplying one-half of the United States’ demand for Mo-99 and one-third of the world’s demand.

A Brighter Future
There has not been a single producer of Mo-99 in the United States for three decades. That will soon change. When the above-mentioned companies begin commercially producing Mo-99, the United States will once again have its own domestic supply of medical radioisotopes. With so many diverse methods for isotope production being explored, the health care industry can look forward to a much more shortage-resistant supply chain. If all goes according to plan, the Mo-99 shortages that plague physicians and patients today will soon be a thing of the past.

— Will Ascenzo is a writer for nuclear technology company Phoenix, LLC, based in Madison, Wisconsin.