Scientists have developed a new system for producing radioactive isotopes, or “radioisotopes” for cancer therapy. The system uses a simple radionuclide generator to repeatedly separate thorium-226 from its longer-lived parent isotope, uranium-230. Both of these isotopes emit radioactive alpha particles. This makes them candidates for use in targeted alpha therapy agents. These are substances that deliver targeted particles to treat disease. The uranium-230/thorium-226 pair has the unique advantage of emitting multiple alpha particles as they decay. This means they can deliver more destructive energy to cancer cells.
Radioisotopes are becoming increasingly critical tools for therapeutic medicine. If researchers have access to more radioisotopes, they can boost the odds of developing therapies for a wide range of cancers. To date, treatments largely rely on beta-emitting isotopes to destroy malignant cells. Alpha particles, emitted by alpha-emitting isotopes, are far more destructive to cells than beta particles. In addition, alpha particles have a short range in the body, so they do much less damage to the surrounding healthy tissue. This also means that alpha emitters can effectively treat cancers that have already spread or metastasized. Researchers have developed several alpha emitters in recent years for “targeted alpha therapy” treatments. These include radium-223/224, actinium-225, and bismuth-213. The uranium-230/thorium-226 pair has the unique advantage of emitting four alpha particles in their decay chain. This means it can deliver more destructive energy to diseased cells. Moreover, production of uranium-230 does not require high energy accelerators, which means it can eventually be produced at a wide variety of sites to increase availability. The thorium-226 generator is easy to set up and is easy for commercial suppliers to deploy at research and medical facilities.
Since the discovery of radium by Marie and Pierre Curie, and the subsequent observation that it could shrink tumors, researchers have sought additional radioisotopes for diagnostic and therapeutic applications. The different chemical and decay properties of individual isotopes make each one uniquely suited to different uses. The Department of Energy’s (DOE) Isotope Program, in the Office of Science, continues to support research in the production of a variety of radioisotopes to increase the number of options for future radioisotope-based treatments. Such is the case for uranium-230 an isotope of uranium. Researchers developed a method to make uranium-230 available to treat diseases by “targeted alpha therapy,” a method that uses alpha-emitting isotopes to treat disease. These isotopes are tethered to biologically compatible compounds to make radioactive drugs or “radiopharmaceuticals” that can be safely injected into the human body and directly transported to the tumor. Other examples of alpha-emitting isotopes produced under the DOE Isotope Program that show promise for targeted alpha therapy include actinium-225 and bismuth-213.
The production of uranium-230 starts with placing thorium metal, which occurs abundantly in nature as thorium-232, in a high energy proton beam. During this process, some of the natural thorium is converted into the isotope proactinium-230. The protactinium-230 decays into uranium-230, which further decays to form an isotope of the element thorium, thorium-226. Both of these isotopes, uranium-230 and thorium-226, have potential for use in radiopharmaceuticals. The apparatus that provides the short-lived thorium-226 daughter from the decay of its longer-lived parent uranium-230 is called a “generator.” A generator uses simple, distinct chemical steps to cleanly separate the parent from the daughter, which gives a continual supply for the next steps in radiopharmaceutical development. DOE Isotope Program researchers are now working on scaled-up production of uranium-230 to make both these isotopes widely available for broader evaluation as potential therapy agents.
This research is supported by the U.S. Department of Energy Isotope Program, managed by the Office of Science.