Hank Hogan and Cory Hatch Idaho National Laboratory
IDAHO FALLS – Beyond X-rays, nuclear medicine involves introducing small amounts of radioactive material into tissues and organs to create detailed images to help diagnose and treat diseases, especially cancer.
Unfortunately, the radioactive components of these materials, called radioisotopes, are often difficult and expensive to produce.
This is especially true for scandium-47, a radioisotope that medical researchers say has great potential as a next-generation theranostic – a radioactive pharmaceutical that can not only diagnose disease, but also treat it. . One gram of the enriched calcium or titanium needed to make scandium-47 can cost thousands of dollars, and global supplies are extremely limited.
Now, for the first time, researchers at the Idaho National Laboratory have used a new technique using high-energy photons to produce scandium-47 from the element vanadium. The project is a collaboration with Jon Stoner and John Longley of the Idaho Accelerator Center at Idaho State University and Tara Mastren of the University of Utah. The results are published in the journal Applied Radiation and Isotopes.
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The manufacture of radioisotopes usually begins with a different and closely related element. This so-called target is then bombarded with subatomic particles in a nuclear reactor or particle accelerator, where it is basically transformed into the desired radioisotope – a process called transmutation.
In the case of calcium- or titanium-enriched targets that are typically used to make scandium-47, the radioisotope produced is not only expensive and rare, but produces a mixture of dangerous scandium isotopes that cannot be chemically purified.
Using vanadium to make scandium-47 is not only cheaper and more widely available than using calcium or titanium targets, but it also produces far fewer unwanted and dangerous scandium isotopes.
The research opens the door to the potential use of scandium-47 as a dual-use diagnostic and therapeutic tool that could be particularly useful in 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 that they haven’t found a way to produce it in very large quantities. The quantities, as well as the impurities, are the two big pitfalls. »
Snow and his colleagues made the discovery as part of radioisotope research conducted for the Defense Threat Reduction Agency. One of the group’s tasks is to produce short-lived isotopes that can be used as training materials for first responders who may need to enter radioactively contaminated environments such as attack sites. terrorists or nuclear accidents.
“One of our projects gave us a very broad license to explore a variety of different reaction pathways to produce short-lived isotopes,” Snow said. “During our research, we came up with the idea of trying to generate extremely pure scandium-47 from natural vanadium. Once we demonstrated it was doable, we realized the breakthrough had significant potential to help the cancer therapy community.
Natural vanadium has several advantages over fortified calcium and titanium as a precursor to scandium-47. First of all, it’s relatively inexpensive. A gram of natural vanadium costs around $30, compared to between $5,000 and $80,000 per gram for fortified calcium and titanium. Second, natural vanadium does not contain as many impurities as calcium and titanium.
Throughout the research and development process, researchers demonstrated the ability to bombard vanadium targets with energetic photons in a linear accelerator and produce 99.998% pure samples. If research progresses for the treatment of cancer, a dedicated accelerator designed in the 20 to 26 million electron-volt range would be able to repeatedly produce this level of purity.
“This research has shown that we can produce scandium-47 with very high purity, possibly the highest in the world,” Snow said.
The technique could also be easy to replicate since linear accelerators are found in many hospitals. Combined with a chemical separation technology recently developed and patented by Snow’s team, the combined method could significantly reduce labor costs and further improve the availability of this isotope to hospitals around the world.
Using the combined production and chemical separation approach developed by Snow’s team, the chemical purification of scandium-47 can be accomplished in just a few hours by a novice technician, unlike traditional approaches, which can require up to a day or more for a highly qualified scientist to accomplish.
The next step is to develop the radioisotope as a theranostic. For this, the INL group is collaborating with Tara Mastren, assistant professor at the University of Utah. “Scandium-47’s short half-life and low energy emissions make it less harmful to non-cancerous tissue than some of the alternatives,” Mastren said.
One option for clinical use is to attach scandium-47 to a biomolecule that targets specific proteins on a patient’s cancer cells, allowing the radioisotope to directly reach diseased tissue. This type of treatment would be tailored to an individual and their specific cancer.
“It kind of acts like a factor,” Mastren said. “It delivers radioactivity to the cancer while minimizing that dose to surrounding healthy tissue.”
During treatment, scandium-47 can provide doctors with a picture of what’s going on inside a patient. “You can imagine where your tracer goes,” Mastren said.
Clinical use will require the manufacture of substantial quantities of scandium-47 for each patient being treated. This problem has not yet been fully resolved, but recent INL research into making the radioisotope in larger quantities is promising. “We have proven in principle that we can manufacture a full therapeutic dose,” Snow said.