ORNL is a leader both in developing advanced radiotherapies and in providing the radioisotopes needed for those therapies.
According to Karen Sikes, director of the National Isotope Development Center, the lab is home to more than 300 isotopes that are available to researchers and others. Besides actinium-225, medical radioisotopes on the list include lead-212, an in vivo alpha emitter generator going through clinical trials for the treatment of liver, prostate, skin and other cancers, and actinium-227, which decays to the alpha emitter radium-223, found in the approved drug Xofigo used to treat prostate cancers that have spread to bone.
"ORNL has a long history of providing medical radioisotopes, going all the way back to 1946," said Jeremy Busby, ORNL's associate laboratory director for isotope science and enrichment.
"It takes time, innovation and the expertise of a lot of trained professionals from many parts of ORNL to safely and successfully produce this next generation of medical radioisotopes, already used in clinical trials and in some approved treatments. I'm proud of our role in making groundbreaking medical advances available to those who need them. I'm excited about other potential radioisotopes and applications for the future."
Sandra Davern, head of ORNL's Radioisotope Research and Development Section, leads two major research initiatives aimed at advancing the use of radioactive isotopes for cancer treatment. The first, launched through ORNL's Laboratory Directed Research and Development program, is called Accelerating Radiotherapeutics through Advanced Molecular Constructs, or ARM. ARM focuses on creating advanced molecular constructs, particularly chelators that enable the labeling of radioisotopes onto targeting molecules under mild, physiologically relevant conditions. This prevents the destruction of sensitive biological molecules, such as antibodies, that would occur with the intense heating required by current technologies.
The second is a Convergent Research Initiative within the University of Tennessee-Oak Ridge Innovation Institute. Called Development and Advancement of Radiopharmaceutical Therapies (DART), it brings together researchers from ORNL, UT and the UT Health Science Center for a five-year, $20 million effort focused on theranostics, which combines targeted alpha therapy and imaging radioisotopes to simultaneously diagnose and treat disease.
To promote theranostics, researchers are also working to design chelators and nanoparticles that can hold either a diagnostic radioisotope or an alpha- or beta-emitting radioisotope.
ORNL chemist Nikki Thiele and colleagues from Washington University in St. Louis, Notre Dame and the University of California at Santa Cruz have made some progress in this direction.
The group published a paper in the journal Chemical Science discussing a chelator called PYTA that can bind at least four relevant radioisotopes, including the alpha emitter actinium-225, the beta emitter lutetium-177, indium-111, which is used in SPECT imaging, and scandium-44, which is used in PET imaging. SPECT imaging refers to Single Photon Emission Computed Tomography, a nuclear medicine imaging technique that uses gamma-emitting radioisotopes (such as indium-111) to generate three-dimensional images of the distribution and function of the tracer inside the body. PET imaging, or Positron Emission Tomography, is a functional imaging technique that detects pairs of gamma rays produced when positrons emitted by a radioisotope (such as scandium-44) annihilate with electrons in tissue, enabling highly sensitive visualization of metabolic and molecular processes.
These research efforts will focus on the radioisotopes as well as everything that gets included with them, both the targeting molecules and the packages holding everything together.
"So, we're looking at new chelators that can hold the radioisotope, looking at nanoparticles, particularly for holding onto the alpha emitters," Davern said. "Because they have decay daughters, and you want to try and hold the parent and those daughters at the cancer site and have less movement to normal tissues.
"And then looking at different targeting molecules for advanced delivery and better penetration of the tumor."
The research is also using artificial intelligence and quantum mechanical computer simulations to help researchers better understand the radioisotopes being used and their behavior within the treatment.
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 .
