Targeted radioactive treatment offers promise in cancer treatment

Los Alamos National Laboratory produces actinium-225 for use in targeted radiotherapy. Early results elsewhere are promising. Courtesy photo

By Kevin John

Cancer is one of the leading causes of death across the world — it is estimated that there will be more than 600,000 cancer deaths in the United States this year. And despite billions of dollars that go toward cancer research, a cure remains elusive. But a radioactive isotope called actinium could be a new breakthrough in cancer research.

What is cancer? Cancer starts when normal cells begin to undergo mutations. The body does a pretty good job of detecting these mutations, or damage to DNA, and repairs it. But when it misses them, cancerous cells can spread into nearby tissues or can metastasize to other organs.

Cancer is hard to cure for many reasons: there are more than 100 types of cancer, the cells evolve and mutate into different types of cancer, cancers can become more resilient and the list goes on and on. Because of these factors, it is unlikely that there can ever be a single cure for all cancer, so new approaches are still needed. Given those constraints, doctors combat cancer in a number of ways, including surgery to remove tumors, radiation and chemotherapy.

An exciting new method is on the horizon. In 2015, the Department of Energy’s Office of Science, Office of Nuclear Physics, Isotope Development and Production for Research and Applications Program launched an unprecedented campaign to develop and provide a supply of actinium-225. It is a rare, radioactive medical isotope that may just hold the cure to some types of cancer. Los Alamos National Laboratory produces actinium-225 for use in targeted radiotherapy and it will soon be tested on volunteer patients. Early results elsewhere are promising.

A radioactive isotope may sound like something that could do more harm than good when it comes to potential cancer treatments, but actinium-225 has proven to be quite effective in the battle against cancer. Actinium-225 can attach to molecules that target only cancer cells, without harming neighboring health cells. In clinical trials treating late-stage prostate cancer patients, it wiped out the cancer in just three treatments. Other clinical trials focused on a variety of cancer types including leukemia, lymphoma, melanoma, glioma and neuroendocrine tumors—and the list is growing.

The interest and demand for actinium-225 continues to grow at a rapid pace due to its great promise in the field of targeted radiotherapy, but previous worldwide supply limited treatment to only a few hundred patients annually.

To remove this limitation, the DOE Isotope Program is leading efforts to find new ways to produce actinium-225 through a number of different production routes. Through the DOE Isotope Program’s Tri-Lab Research effort to provide accelerator-produced actinium-225 for the radiotherapy project, Los Alamos, Oak Ridge National Laboratory and Brookhaven National Laboratory have developed a new promising process that can produce very large quantities of this hard-to-make isotope in full support of clinical trials and for development of large-scale treatments. Starting this year, the medical community has had access to this increased supply.

Only a few accelerators in the world can create high-enough-energy proton beams to generate actinium-225. One of those is the Los Alamos Neutron Science Center (LANSCE). While most of the work done at LANSCE focuses on national security science, it creates plenty of powerful protons for producing isotopes that the DOE Isotope Program then utilizes.

This new actinium-225 production process starts with a target made of natural thorium metal formed into a disk that is about the size of a hockey puck. Scientists place the disk in the proton beam path, which accelerates protons up to about 40 percent the speed of light. As the protons hit the thorium, they transfer their energy to the protons and neutrons in the thorium target. The protons and neutrons that gain enough kinetic energy escape the thorium atom.

The process of expelling protons and neutrons transforms the thorium atoms into hundreds of different elements and isotopes, including actinium-225. After days of bombardment from these high-energy protons, the thorium disk is removed from the beam. After a short rest to allow some very short-lived radioisotopes to decay, reducing total radioactivity, the target is sent to Oak Ridge to purify the actinium-225 into a useful form for further research.

This new process could produce up to 20 times more actinium-225 than before. Significant amounts of accelerator-produced actinium-225 have been distributed for pre-clinical evaluation and to doctors across the world, including at the University of New Mexico, where they are preparing to start the first human trial using DOE Isotope Program-produced actinium-225.

Kevin John is the Chemistry Deputy Division Leader at Los Alamos National Laboratory and Ac-225 Tri-Lab Project Manager.

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