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INL-led research team finds a better way to make cancer-fighting isotope

Researchers from Idaho National Laboratory (INL) and two universities have developed a novel technique to produce scandium-47 - a radioisotope used in nuclear medicine - more easily and less expensively than existing methods.

A step beyond X-rays, nuclear medicine involves introducing small amounts of radioactive materials into tissues and organs to make detailed images for diagnosing and treating diseases, especially cancer. Unfortunately, the radioactive building blocks of these materials, called radioisotopes, are often difficult and expensive to produce.

That’s especially true for scandium-47, a radioisotope that medical researchers say has big potential as a next-generation theranostic – a radioactive pharmaceutical that can not only diagnose disease but treat it as well. One gram of the enriched calcium or titanium needed to make scandium-47 can cost thousands of dollars, and worldwide supplies are extremely limited.

Now, for the first time, INL researchers have used high energy photons to produce scandium-47 from the element vanadium. The project is a collaboration with Jon Stoner and John Longley from the Idaho State University's Idaho Accelerator Center and Tara Mastren from the University of Utah. The results wee published last month in the journal Applied Radiation and Isotopes.

Making radioisotopes typically starts with a different, closely related element. That so-called target is then bombarded with subatomic particles in a nuclear reactor or a particle accelerator, where it is fundamentally changed into the desired radioisotope – a process called transmutation.

In the case of enriched calcium or titanium targets that are typically used to make scandium-47, the radioisotope produced is not only expensive and rare, but it yields a mixture of hazardous scandium isotopes that cannot be chemically purified.

Using vanadium to make scandium-47 is not only less expensive and more widely available than using calcium or titanium targets, but it also produces far fewer unwanted, hazardous scandium isotopes.

The research opens the door for potential use of scandium-47 as a dual-purpose diagnostic and therapeutic tool that could be especially useful for diagnosing and treating neuroendocrine tumors or prostate cancers.

“The medical community has known for some time that scandium-47 has valuable theranostic properties,” said Mathew Snow, a radiochemist and program manager at INL who led the project. “The main problem is they haven’t been able to find a way to produce it in very large quantities. The quantities, as well as the impurities, are the two big showstoppers.”

Snow and his colleagues made the discovery as an offshoot of radioisotope research being conducted for the Defense Threat Reduction Agency. One of the group’s jobs is to produce short-lived isotopes that can be used as training materials for first responders who might need to enter radioactively contaminated environments such as terrorist attack sites or nuclear accidents.

“One of our projects gave us very broad license to explore a variety of different reaction pathways to produce short-lived isotopes,” Snow said. “During the course of our research, we had the idea to try to generate extremely pure scandium-47 from natural vanadium. Once we demonstrated that it was feasible, we realized the breakthrough had significant potential to help the cancer therapy community.”

Natural vanadium has several benefits over enriched calcium and titanium as a precursor to scandium-47. First, it’s relatively inexpensive. One gram of natural vanadium costs about $30, compared with between $5000 and $80,000 a gram for enriched calcium and titanium. Second, natural vanadium does not contain as many impurities as calcium and titanium.

Throughout the research and development process, the researchers demonstrated the ability to bombard vanadium targets with energetic photons in a linear accelerator and produce samples as high as 99.998% pure. If the research moves forward for cancer therapy, a dedicated accelerator designed in the 20-26 million electron volts range would be able to repeatably produce this level of purity.

“This research has shown that we can produce scandium-47 in very high purity, maybe the highest in the world,” Snow said.

The technique might also be easy to replicate since linear accelerators are found in many hospitals. When combined with a chemical separation technology recently developed and patented by Snow’s team, the combined method could drastically cut down on labor costs and further improve the availability of this isotope to hospitals around the world.

Using the combined production-chemical separation approach developed by Snow’s team, chemical purification of the scandium-47 can be accomplished in only a few hours by an entry level technician as opposed to traditional approaches, which can require up to a day or more for a highly skilled scientist to accomplish.

The next step is to develop the radioisotope as a theranostic. For that, the group at INL is collaborating with Mastren, an assistant professor at the University of Utah.

“Scandium-47’s short half-life and low energy emissions make it less harmful to noncancerous tissue than some of the alternatives,” Mastren said.

One option for clinical use is to attach the scandium-47 to a biomolecule that targets specific proteins on a patient’s cancer cells, allowing the radioisotope to go directly to the diseased tissue. This type of treatment would be tailored to an individual and his or her specific cancer.

“It kind of acts like a mailman,” Mastren said. “It delivers radioactivity to the cancer while minimizing that dose to healthy, surrounding tissue.”

During treatment, scandium-47 can provide doctors with a picture of what is happening inside a patient. “You can image where your tracer is going,” Mastren said.

Clinical use will require making substantial quantities of scandium-47 for every patient in treatment. That problem has not been entirely solved yet, but recent INL research on making the radioisotope in larger amounts is promising.

“We proved in principle that we could make a whole therapeutic dose,” Snow said.

Read more: https://inl.gov/article/security-researchers-discover-abundant-cost-effe...

Read the study: https://www.sciencedirect.com/science/article/abs/pii/S0969804321003316

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