An ORNL project is focused on harnessing the power of very low-energy electrons for an isotope-based cancer treatment.
Led by Dr. Nikki Thiele of the Physical Sciences Directorate, the research deals with targeted radiotherapy by ions that emit Auger electrons. Co-investigators are Dr. Sandra Davern and Dr. Miguel Toro-Gonzalez of the Isotope Science and Engineering Directorate, Dr. Alex Ivanov of the Physical Sciences Directorate, and Dr. Jonathan Engle of the University of Wisconsin-Madison.
The researchers’ goal is to be able to attach radioactive metal ions that emit Auger electrons — very low-energy electrons — to a biological vector that can seek out and target cancer cells. In order to do that, they must find molecules — chelators — that can bind the isotopes that will irradiate cancerous cells to the vectors that will carry them to those cells.
In this case, they’re exploring the development of molecules to bind the Auger-emitting radioisotope antimony-119, Sb-119, which is produced by generators currently supported by the DOE Isotope Program. Thiele said the short penetration range — less than half the diameter of a human cell — and high linear energy transfer of Auger electrons emitted by Sb-119 means it could be used to eradicate very small clusters of cancer cells or even single cancer cells with little irradiation to surrounding healthy tissue. The development of precision treatments for these types of cancers represents an unmet clinical need in oncology medicine.
Thiele said irradiating cancer cells with Auger electron emissions is one alternative to the better-known targeted therapies using alpha and beta radiation, which deposit energy over relatively longer ranges and therefore are useful in treating larger clusters of cancer cells. Recent advances in isotope production have made feasible the routine production of several Auger-emitting isotopes, leading to a resurgence of interest in targeted Auger therapy as a promising strategy to treat cancer, she said.
“It’s exciting to be expanding our efforts to develop chelators for medical isotopes here at ORNL,” Thiele said. “This is an opportunity to propel an emerging Auger emitter, Sb-119, into clinical studies by developing binding molecules that can support its use in nuclear medicine.”
Thiele, whose area of expertise is coordination chemistry, joined ORNL more than two years ago. She works on designing and developing molecules to selectively bind radioactive and non-radioactive ions that are relevant to medical and clean energy applications. She said she’s proud the team’s proposal has garnered funding from DOE, especially since the competition was fierce. The projects were selected by competitive peer review under the DOE Funding Opportunity Announcement for FOA 2532: Advancing Novel Medical Isotopes for Clinical Trials, in cooperation with the National Institutes of Health, which assessed proposals.
“It’s a major accomplishment,” she said.
Their research is part of a $1 million U.S. Department of Energy funding initiative, DOE announced recently. ORNL and the University of Wisconsin-Madison will share the award, intended to advance research and development of emerging medical isotopes into preclinical and clinical trials, with researchers from University of California-San Francisco.
Total funding is $1 million for awards lasting up to two years, with outyear funding contingent on congressional appropriations. The funding, administered by DOE, is part of a key federal program that produces critical isotopes otherwise unavailable or in short supply for U.S. science, medicine and industry.
In addition to potential cancer therapies, radioisotopes — atoms with excess energy in their nucleus — are also used widely for medical imaging and diagnostic procedures. Certain isotopes already are in use for the treatment of cancer and other diseases.
“The novel isotopes produced by the DOE Isotope Program can enable transformative approaches to cancer treatments with levels of efficacy that have not been seen before, as well as innovative technologies for imaging of disease and the human body,” said Jehanne Gillo, director of the DOE Isotope Program. “It is essential to advance these isotopes for use in preclinical and clinical trials, as they have potentially enormous benefits to the field of modern medicine.”
UT-Battelle manages ORNL for the Department of Energy’s Office of Science, the single largest supporter of basic research in the physical sciences in the United States. The Office of Science is working to address some of the most pressing challenges of our time. For more information, please visit energy.gov/science.
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