The challenges: According to an October 20 LLNL news release, actinium-based cancer therapies could be hundreds of times more effective than current drugs. Radioactive isotopes typically must be purified through lengthy separation processes, however, and must have a stable chelating agent designed to bind to the radioactive ions to control toxicity in the human body.
“These challenges exist even for medical isotopes in relatively widespread use, such as radioactive yttrium, but they are even more taxing in the case of actinium,” said LLNL scientist Gauthier Deblonde, lead author of a paper published on October 20 in the journal Science Advances.
While actinium is a naturally occurring element, it is rare, and actinium-225—the isotope used for medical applications—must be produced in nuclear reactors or other large and costly instruments before it is purified. Research into actinium chemistry has so far focused on reusing or adapting similar known synthetic molecules used in nuclear chemistry, with limited results.
Penn State protein discovery is key: In 2018, Penn State researchers discovered a natural protein called lanmodulin, which can improve and simplify the purification processes for actinium and could also be used to recover and detect other radioactive elements.
“In this study, our team took advantage of a protein my lab previously discovered called lanmodulin and showed that it can be used to improve and simplify the recovery and purification of actinium,” said Joseph Cotruvo Jr., assistant professor of chemistry at Penn State and an author of the paper, in a news release issued by Penn State, also on October 20. “We believe that our results unify the fields of metal separations and biochemistry and have strong potential to revolutionize several critical steps in medicinal chemistry—from purifying isotopes to delivering therapeutic doses to patients.”
Key results: The team showed how lanmodulin can be used to bind, recover, and purify actinium, as well as another medically relevant radioisotope, yttrium-90, which is used for cancer therapy and diagnostics. The protein-based purification approach reportedly yielded at least 99.5 percent purity in a single step, allowing for the preparation and research of actinium at a much lower cost. The researchers found that lanmodulin specifically binds actinium even in the presence of large quantities of process impurities and is more effective at binding actinium than binding to the rare earth elements it is associated with in nature. The researchers believe that the process is likely extendable to other radioactive isotopes used in radiation therapy and imaging.
“Our approach, that combines lanmodulin’s tight and specific binding with inexpensive filtration devices, allowed us to easily access minute quantities of radiometals, as low as a few attograms, where traditional technologies based on synthetic chelators fail,” Deblonde said. “What we accomplished here was simply unfathomable a few years ago.” One attogram is one billionth of a billionth of a gram, about the weight of a single virus particle. In this case, it corresponds to the weight of just about 3,000 atoms of actinium.
The team: In addition to Deblonde and Cotruvo, the research team included LLNL researchers Ziye Dong, Paul Wooddy, and Mavrik Zavarin, and Penn State graduate student Joseph Mattocks. The work was funded by LLNL’s Laboratory Directed Research and Development program and the Department of Energy’s Office of Science.
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