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LANL’s Isotope Research Opens New Possibilities for Cancer Treatment

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A new study at Los Alamos National Laboratory (LANL), in collaboration with Stanford Synchrotron Radiation Lightsource, is giving scientists a new understanding of how the element actinium could help create innovative new classes of anticancer drugs.

“The short half-life of actinium-225 offers opportunity for new alpha-emitting drugs to treat cancer, although very little has been known about actinium because all of its isotopes are radioactive and have short half-lives,” said Maryline Ferrier, a Seaborg post-doctoral researcher on the LANL team. “This makes it hard to handle large enough quantities of actinium to characterize its chemistry and bonding, which is critical for designing chelators.”

These new insights could provide the chemical information researchers need to develop ways to bind actinium so that it can be safely transported through the body to the tumor cell. “To build an appropriate biological delivery system for actinium, there is a clear need to better establish the chemical fundamentals for actinium,” Ferrier said. “Using only a few micrograms (approximately the weight of one grain of sand) we were able to study actinium-containing compounds at the Stanford Synchrotron Radiation Lightsource and at Los Alamos, and to study actinium in various environments to understand its behavior in solution.”

Researchers have long used LANL’s specialty facilities—like the linear particle accelerator at the Los Alamos Neutron Science Center (LANSCE)—to provide rare and important isotopes to the medical community across the United States for medical scans. Now, Ferrier said, exploring actinium moves the research forward toward treatment isotopes, as opposed to only diagnostic materials.

Researchers used a spectroscopic analysis called X-ray absorption fine structure (XAFS), which can determine chemical information such as the number of atoms surrounding actinium, their type (i.e., oxygen or chlorine), and their distances from each other. To understand actinium’s behavior in solution and interpret the data obtained with XAFS, they compared these experimental results with sophisticated computer model calculations using molecular-dynamics density functional theory (MD-DFT).

Results showed that actinium, in solutions of concentrated hydrochloric acid, is surrounded by three atoms of chlorine and six atoms of water. Americium, another +3 actinide often used as a surrogate for actinium, is surrounded by one chlorine atom and eight water molecules. It has been assumed in the past that actinium would behave similarly to americium.

“Our study shows that the two are different in a way that could help change how actinium ligands are designed,” Ferrier said.

Perhaps the most potent impact of these studies will be on the application of the isotope actinium-225, which is used in a novel, attractive cancer treatment technique called targeted alpha therapy (TAT). TAT exploits alpha emissions from radioisotopes to destroy malignant cells, while minimizing the damage to healthy surrounding tissue. “Our determination that actinium’s behavior in solution is different than other nearby elements (such as americium) is directly relevant to TAT in a biological environment,” said Ferrier.

Actinium-225 has a relatively short half-life (10 days) and emits four powerful alpha particles as it decays to stable bismuth, which makes it a perfect candidate for TAT. However, TAT with actinium can become a reliable cancer-treatment only if actinium is securely bound to the targeting molecule, as the radioisotope is very toxic to healthy tissue if it is not brought quickly to the site of disease.

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